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| Intervention | Disease | N | Report | Tissue | Assay | Treg change | Result | Confidence | Bias & confounding | Source | PMID | Design | Dose/schedule | Treg defn | Readout | Timepoint | Timing detail | Baseline | Post | Magnitude | Significance | Durability | Intent | Data source | Notes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Denileukin diftitox (ONTAK) | Metastatic melanoma | 13 | J Immunother, 2005 | PBMC | flow | ≈ n.s. | null result null | Moderate | Low small-nunderpowered | PMID PMCID DOI critique | 16224276 | paired-pre-post | Variable per prior dosing schedules | CD4+CD25+FOXP3+ | frequency-of-CD4 | early-on-treatment | post-dose serial sampling | Not reported in cells/µL; FoxP3 mRNA expression (copies/10^3 β-actin) only | FoxP3 mRNA change (cycle 1): 9 µg/kg cohort −1.27±2.57 (p=0.656, n=4); 18 µg/kg cohort −2.01±0.618 (p=0.031, n=5); pooled −1.68±1.11 (p=0.167, n=9); after ≥4 cycles (n=4) −3.30±3.21 (p=0.380) | Small, dose-dependent FoxP3 mRNA reduction; no elimination of CD4+CD25+ cells; suppressive function preserved (50.6-98.2% suppression retained in 5 patients post-cycle-2) | p=0.031 (18 µg/kg only); pooled n.s. | — | mechanism-targeted | pmc_full_text | Attia 2005 — key null result: DAB/IL-2 failed to eliminate functional Tregs in melanoma. Full-text backfill 2026-04-23: statistically significant FoxP3 mRNA decrease only in 18 µg/kg cohort (p=0.031), pooled analysis n.s. (p=0.167); in vitro suppression retained in 5/5 patients (50.6-98.2%). Conflicts with Dannull 2005 (16308572): Dannull saw d4 functional abrogation in RCC while Attia saw preserved suppression post-cycle-2 in melanoma; gating (FOXP3+ vs CD4+CD25+) and timepoint differences likely reconcile. |
| Denileukin diftitox (DAB389IL-2) prior to RCC tumor-RNA DC vaccineAutologous RCC tumor-RNA dendritic cell vaccine | Metastatic renal cell carcinoma | 11 | J Clin Invest, 2005 | PBMC | flow+fn | ↓ −51% | significant reduction depletion | Low | Moderate cd25-gating-confoundsmall-nno-multiplicity-correction | PMID PMCID DOI critique | 16308572 | paired-pre-post | Single infusion prior to vaccination | CD4+CD25+ (functional Treg assay) | frequency-of-CD4 | early-on-treatment | pre- and post-denileukin diftitox; then post-vaccine | 2.5-4.6% CD4+CD25high/FoxP3+ of CD4+ (2.1±1.2-fold above healthy volunteers n=10) | 26-76% relative reduction of CD4+CD25high Tregs at day 4 post-DAB389IL-2 (all 7 subjects analyzed) | 26-76% reduction in CD4+CD25high; FoxP3 mRNA reduced ~30-80% within purified CD4+ cells at day 4 | reported significant (all 7 subjects) | Transient: ~75% of Tregs restored within 2 months (d4 nadir, d60 recovery) | mechanism-targeted | pmc_full_text | Dannull 2005 JCI — first clear demonstration that DAB389IL-2 depletes functional Tregs in cancer patients and enhances vaccine response. Full-text backfill 2026-04-23: explicit 26-76% range for frequency reduction, 30-80% for FoxP3 mRNA, nadir d4, 75% recovery by 2 months, suppressive function abrogated. |
| Low-dose oral cyclophosphamide (metronomic) | Advanced end-stage solid cancers | 9 | Cancer Immunol Immunother, 2007 | PBMC | flow | ↓ −61% | significant reduction depletion | Moderate | Moderate very-small-nsingle-arm-no-control | PMID PMCID DOI critique | 16960692 | paired-pre-post | 50 mg PO twice daily, 1 week on / 1 week off | CD4+CD25highFOXP3+ | frequency-of-CD4 | early-on-treatment | after 1 month (day 28-ish) | 7.9 ± 1.5% (CD4+CD25high of CD4+); 28.7 ± 9.4 cells/mm3 (absolute) | 3.1 ± 1.8% (CD4+CD25high of CD4+); 6.4 ± 5.4 cells/mm3 (absolute) at 1 month | ~61% reduction in frequency (7.9% to 3.1%) and ~78% reduction in absolute count (28.7 to 6.4 cells/mm3) | p<0.0001 (both frequency and absolute count) | Maintained during metronomic dosing; 2/2 patients with extended follow-up had Treg return to pretreatment levels ~2 months after stopping CTX | mechanism-targeted | pmc_full_text | Landmark Ghiringhelli 2007 metronomic-cyclo PD paper. Full-text backfill 2026-04-23: explicit mean±SD frequency and absolute count values, p<0.0001 for both, functional recovery data, 2-month off-treatment recovery. Side-list Ghiringhelli 2004 preclinical excluded from table. |
| Daclizumab (anti-CD25) | Metastatic melanoma | 8 | Int J Cancer, 2007 | PBMC | flow | ↓ sig. | significant reduction depletion | Low | Moderate cd25-gating-confoundabstract-onlyvery-small-nsurface-marker-gating | PMID DOI critique | 17315189 | paired-pre-post | Single bolus, then successive | CD4+CD25+ (FOXP3-validated in subset) | frequency-of-CD4 | early-on-treatment | immediately post-first bolus through day 13 | — | — | significantly reduced; successive doses further reduced | reported significant | Recovery observed over ~13 days after single dose; sustained with repeated dosing | mechanism-targeted | pubmed_abstract | Mahnke 2007 — daclizumab Treg depletion kinetics. Full-text backfill 2026-04-23: not openly accessible (Int J Cancer, inEPMC=N, subscription required). Abstract-only values retained: significant PBMC Treg reduction after single bolus, sustained with repeat dosing, ~13-day recovery window. |
| Single IV cyclophosphamide + intratumoral BCGIntratumoral BCG (non-specific immunotherapy) | Metastatic solid cancer (mixed) | 49 | Clin Exp Immunol, 2007 | PBMC | flow | ≈ n.s. | null result null | Low | Moderate abstract-onlysurface-marker-gating | PMID critique | 17956583 | treated-vs-untreated | Single IV dose (300 mg/m2 per paper) | CD4+CD25+ (FoxP3 referenced) | frequency-of-CD4 | early-on-treatment | post-infusion serial | 9.2% | not significantly changed | baseline 9.2% (patients) vs 7.1% (healthy) — post-cyclo: no significant modulation | n.s. | — | mechanism-targeted | pubmed_abstract | Audia 2007 — single-dose IV cyclo + BCG failed to modulate Treg numbers or function despite elevated baseline in cancer patients. Important null result anchoring the 'dose schedule matters' argument. Full-text backfill 2026-04-23: article not openly accessible (not in PMC, Europe PMC inEPMC=N, subscription required). Abstract-derived baseline 9.2% vs 7.1% healthy and 'no significant modulation' remains the only numeric available. |
| Tremelimumab | Melanoma | 13 | J Transl Med, 2008 | PBMC | flow | ≈ n.s. | null result null | Moderate | Moderate small-nno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI critique | 18452610 | paired-pre-post | Per trial | CD4+CD25highFOXP3+ | frequency-of-CD4 | early-on-treatment | Serial post-infusion | FoxP3 mRNA pre-dose (qPCR); per-patient values not tabulated | No statistically significant change between pre- and post-dosing FoxP3 mRNA (n=8 evaluable of 13) | No significant change in FoxP3 mRNA pre→post; insufficient cells for functional suppression assay | n.s. (p-value not stated) | — | exploratory-but-prespecified | pmc_full_text | Comin-Anduix 2008 — PBMC PD of tremelimumab. Full-text backfill 2026-04-23: n=8 with baseline+follow-up FoxP3 mRNA data; 'failed to detect a statistically significant change (either positive or negative)'; Treg functional assay not performed due to insufficient cells from 40 mL draws. |
| Daclizumab (anti-CD25) prior to CEA-based cancer vaccineCEA-targeted cancer vaccine | Advanced CEA-expressing cancers (mixed solid) | 15 | Blood, 2008 | PBMC | flow | ↓ sig. | significant reduction depletion | Moderate | Moderate cd25-gating-confoundsmall-nschedule-dependent | PMID PMCID DOI critique | 18519811 | paired-pre-post | Multiple doses | CD4+CD25highFoxP3+ | frequency-of-CD4 | early-on-treatment | pre- and post- multi-dose daclizumab; then post-vaccine | Baseline CD4+CD25highFoxP3+ frequency (absolute µL count) not tabulated; per-patient trajectories shown in figures | Cohort 2 (multi-dose, n=4): all 4 patients had lower Treg % at study end; Cohort 1 (single-dose, n=5): only 2/5 reduced | Dose-schedule dependent: multi-dose DD → 4/4 reduction; single-dose DD → 2/5 reduction; absolute Treg counts per µL began declining at week 5 and continued after final vaccination (Cohort 2 only) | Time-to-first immune response p=0.003 (Cohort 2 vs Cohort 0); individual Treg p-values not reported | Multi-dose sustained decline through post-vaccine follow-up; single-dose rebounded | mechanism-targeted | pmc_full_text | Morse 2008 Blood — pilot vaccine study. Full-text backfill 2026-04-23: schedule-dependent depletion confirmed (4/4 multi-dose vs 2/5 single-dose reduced Treg%); absolute µL counts only in Cohort 2. No tabulated baseline/post numeric means. Conflict pair with Luke 2016 (27330808): both show single-dose DD fails; Morse shows multi-dose DD succeeds — not a true conflict but a schedule-dependence finding. |
| Ipilimumab or tremelimumab | Melanoma | 11 | Clin Cancer Res, 2009 | tumor | flow | ≈ n.s. | null result null | Low | Serious retrospective-analysisfoxp3-ihc-single-markerabstract-onlyvery-small-n+1 | PMID DOI critique | 19118070 | paired-pre-post | Per trial | FoxP3+ | frequency-of-lymphocytes | early-on-treatment | Post-dose biopsy | — | — | No consistent FoxP3 reduction post-CTLA-4 blockade | n.s. | — | exploratory-but-prespecified | pubmed_abstract | Ribas 2009 — intratumoral FoxP3/IDO in CTLA-4 blockade. Full-text backfill 2026-04-23: Clin Cancer Res article not in Europe PMC OA (inEPMC=N, subscription required). Abstract retains qualitative 'no consistent FoxP3 reduction' finding supporting early null-for-intratumoral-depletion; numeric values not extractable. |
| Denileukin diftitox (DD) + high-dose IL-2High-dose IL-2 | Metastatic renal cell carcinoma | 18 | J Immunother, 2010 | PBMC | flow | ↓ −56.3% | significant reduction depletion | Low | Serious cd25-gating-confoundabstract-onlysurface-marker-gatingretrospective-analysis+1 | PMID DOI critique | 20664355 | paired-pre-post | Groups A/B/C dose-escalation | CD4+CD25+ | frequency-of-CD4 | early-on-treatment | pre-DD to post-DD, serial | — | — | median 56.3% reduction from pre-DD to post-DD | p=0.013 | — | mechanism-targeted | pubmed_abstract | Atchison 2010 pilot. Clean median 56.3% reduction from pre-DD to post-DD, p=0.013 (abstract-reported). Full-text backfill 2026-04-23: article not openly accessible (J Immunother, inEPMC=N, subscription required); abstract numeric retained as sole source. |
| Tremelimumab (anti-CTLA-4) | Metastatic melanoma | 18 | Clin Cancer Res, 2011 | tumor | flow | ↑ +375% | increase null | Moderate | Moderate foxp3-ihc-single-markersmall-nno-multiplicity-correctionauthor-coi-sponsor | PMID PMCID DOI critique | 21558401 | paired-pre-post | Per trial schedule | FOXP3+ | frequency-of-lymphocytes | early-on-treatment | Post-dose biopsy | 35.20 ± 30.06 FOXP3+ cells/mm^2 (n=19 paired) | 167.35 ± 162.37 FOXP3+ cells/mm^2 post-dosing | Mean +132.15 cells/mm^2 (~4.75× INCREASE) in FOXP3+ density; CR patients 993.76±734.18 vs PD 775.63±458.70 (n.s. p=0.3340) | p=0.0029 (paired Mann-Whitney; note: paper uses paired test despite Mann-Whitney label) | — | mechanism-targeted | pmc_full_text | Huang 2011 — tremelimumab INCREASED rather than depleted intratumoral FOXP3+ cells. Full-text backfill 2026-04-23: baseline 35.2 → post 167.4 cells/mm^2 (p=0.0029, paired, n=19). Classic early null-for-intratumoral-Treg-depletion result supporting Sharma 2019's broader conclusion. |
| Ipilimumab (in patients with severe enterocolitis) | Melanoma (with ipi-induced enterocolitis) | 4 | Inflamm Bowel Dis, 2012 | other | flow | ↓ qual. | significant reduction depletion | Very low | not amenable — case report case-report-n-of-fewabstract-onlyspin-abstract-vs-results | PMID DOI critique | 22069060 | case-series | Per trial | FoxP3+ | frequency-of-lymphocytes | late | At time of colitis flare | — | — | Profound long-lasting FoxP3+ Treg depletion in colonic mucosa | reported | Long-lasting | incidental-but-measured | pubmed_abstract | Nancey 2012 — ipi-enterocolitis colonic mucosa Treg depletion. Full-text backfill 2026-04-23: Inflamm Bowel Dis article not in Europe PMC OA (inEPMC=N, subscription required). Abstract retains 'profound long-lasting FoxP3+ Treg depletion' in lamina propria; numeric density values not extractable from abstract. |
| Ipilimumab | Advanced melanoma (stage III/IV) | 82 | J Transl Med, 2011 | tumor | flow | — | null result null | Low | Moderate exploratory-endpointno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI critique | 22123319 | paired-pre-post | Per trial | FoxP3+ | frequency-of-lymphocytes | early-on-treatment | Baseline vs week 3 (24-72h post-dose 2) | Benefit group: FoxP3 detected in 75.0% of evaluable pretreatment biopsies; Non-benefit group: 36.0% | Longitudinal change not quantified — paper reports baseline FoxP3 only as predictive biomarker | Not a depletion study; baseline FoxP3 positivity associated with clinical benefit (OR ~10.38, p=0.014); TIL increase post-dose separate finding (p=0.005) | p=0.014 (baseline FoxP3 vs clinical benefit); not a post-treatment-change p-value | — | incidental-but-measured | pmc_full_text | Hamid 2011 — predictive biomarker study, NOT a depletion endpoint. Full-text backfill 2026-04-23 confirmed: FoxP3 quantified only at baseline (pretreatment biopsy), not longitudinally; 24-72h post-dose-2 samples collected but FoxP3 change not quantified. Reclassified intent_to_deplete from 'exploratory-but-prespecified' to 'incidental-but-measured' — the study did not aim to measure Treg depletion. Retained in table because it still reports a Treg-related readout in melanoma ipi patients. |
| Azacitidine + panobinostatazacitidine (DNMTi) + panobinostat (HDACi) | Acute myeloid leukemia | 14 | Clin Cancer Res, 2014 | PBMC | flow | ↓ sig. | significant reduction depletion | Moderate | Moderate abstract-onlysmall-n | PMID DOI critique | 24297862 | paired-pre-post | panobinostat + azacitidine 28-day cycles (dose not specified in abstract) | CD4+CD25hi FOXP3+ TNFR2+ subset | frequency-of-CD4 | mid | after 28-day cycle(s) of aza+pano | elevated vs healthy donors (TNFR2+ Treg subset) | decreased in vivo after aza+pano | TNFR2+ Treg reduction (no numeric % given in abstract) | reported significant; associated with increased IFN-γ, IL-2 and clinical benefit | measured within 28-day cycles | pre-specified-endpoint | pubmed_abstract | Govindaraj 2014 CCR. Abstract-only — no PMC record (non-OA in 2014 CCR). The reduction is specifically in TNFR2+ Treg subset, not total FoxP3+ Tregs. Panobinostat identified as the primary Treg-reducing agent in combination. Important conceptual anchor for HDACi-driven Treg-subset targeting in AML. |
| Azacitidine + panobinostatazacitidine (DNMTi) + panobinostat (HDACi) | Acute myeloid leukemia | 14 | Clin Cancer Res, 2014 | bone-marrow | flow | ↓ sig. | significant reduction depletion | Moderate | Moderate abstract-onlysmall-n | PMID DOI critique | 24297862 | paired-pre-post | panobinostat + azacitidine 28-day cycles (dose not specified in abstract) | CD4+CD25hi FOXP3+ TNFR2+ subset | frequency-of-CD4 | mid | after 28-day cycle(s) of aza+pano | elevated vs healthy donors, high BM-migration potential | decreased in vivo after aza+pano | TNFR2+ Treg reduction in bone marrow (no numeric % in abstract) | reported significant; associated with increased IFN-γ, IL-2 in bone marrow effector T cells | — | pre-specified-endpoint | pubmed_abstract | Govindaraj 2014 CCR — bone-marrow companion row to the PBMC row. Same caveats: abstract-only, no numerics, TNFR2+ subset not total FoxP3+. |
| Single-dose denileukin diftitox + gp100:209-217(210M) peptide vaccinegp100:209-217(210M) peptide vaccine + IFA + IL-2 | Advanced melanoma | 60 | J Immunother Cancer, 2016 | PBMC | flow | ≈ n.s. | null result null | Low | Moderate cd25-gating-confoundindustry-sponsored | PMID PMCID DOI critique | 27330808 | randomized-controlled | Single dose pre-vaccine | CD4+CD25highFoxP3+ | frequency-of-CD4 | early-on-treatment | pre-vaccine post-DD | Not numerically reported; individual patient data shown in Fig 2 without quantification | Not reproducibly reduced; frequencies similar to control patients | No reproducible reduction in peripheral Treg numbers; 1/1 evaluable paired tumor biopsy (patient 16) showed INCREASED FoxP3 transcripts post-DD | n.s. (no depletion) | — | mechanism-targeted | pmc_full_text | Luke 2016 RCT — single-dose DD failed to deplete Tregs or enhance vaccine responses. Full-text backfill 2026-04-23: no numeric baseline/post Treg values in text (Fig 2 unquantified); 1 paired tumor biopsy showed INCREASED intratumoral FoxP3 post-DD. Conflict pair with Morse 2008 (18519811): Luke=single-dose→fail; Morse=multi-dose→succeed. Reconciled by schedule dependence, not truly conflicting. |
| Entinostat + high-dose IL-2entinostat (HDACi, class I) + high-dose IL-2 | Metastatic clear-cell renal cell carcinoma | 12 | Clin Cancer Res, 2017 | PBMC | flow | ↓ sig. | nonsignificant trend depletion | Moderate | Some concerns surface-marker-gatingno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 28939740 | paired-pre-post | entinostat oral priming C1D-14 through C1D1; HD IL-2 standard | CD4+CD25hi T cells | frequency-of-CD4 | early-on-treatment | C1D1 (post-priming entinostat, pre-IL-2) | pretreatment CD4+CD25hi frequency (not numeric in manuscript) | statistically significant decline in responders (n=5) vs progressors (n=7) | Treg frequency lower at C1D1 in responders (p=0.0273) | p=0.0273 responders lower than progressors at C1D1; p=0.03 lower Treg overall associated with response | measured across priming phase only (2 weeks entinostat) | mechanism-targeted | pmc_full_text | Pili 2017 CCR. PMC full text (PMC5712266). Class I HDACi entinostat was explicitly selected to downregulate FOXP3 and Treg suppressive function (preclinical rationale). Clinical data show a modest response-associated Treg decline, but absolute numerics are not reported for the whole cohort — only 12 of 47 had complete Treg samples. Design: priming phase (entinostat alone for 2 weeks) then combined with HD IL-2. |
| Entinostat + high-dose IL-2entinostat (HDACi, class I) + high-dose IL-2 | Metastatic clear-cell renal cell carcinoma | 3 | Clin Cancer Res, 2017 | tumor | flow | mixed | nonsignificant trend depletion | Moderate | Some concerns surface-marker-gatingno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 28939740 | paired-pre-post | entinostat oral priming C1D-14 through C1D1; HD IL-2 standard | CD4+FOXP3+ (IHC) | other | early-on-treatment | post-entinostat 2-week priming; before HD IL-2 | pretreatment tumor Treg infiltration | stable or decreased Treg infiltration in 3 paired biopsies | stable or decreased (no quantitative increase despite HD IL-2 co-administration) | not tested | — | mechanism-targeted | pmc_full_text | Pili 2017 CCR — tumor biopsy companion row, N=3 only. Value of row is that HD IL-2 alone is known to expand Tregs; entinostat priming prevented that expansion in the intratumoral compartment. Not statistically powered. |
| Neoadjuvant chemotherapy + ipilimumabNeoadjuvant chemotherapy + ipilimumab | Early-stage NSCLC (IB-IIIA) | 24 | Clin Cancer Res, 2017 | PBMC | flow | ↑ sig. | increase null | Low | Moderate small-npbmc-only-generalizedno-multiplicity-correction | PMID PMCID DOI critique | 28951518 | window-of-opportunity | Per trial | CD4+FOXP3+ | frequency-of-CD4 | early-on-treatment | Baseline vs post-neoadjuvant | Per-patient baseline; aggregate not tabulated | Median frequency of CD4+CD25+FOXP3+ Tregs increased slightly by 1.05% (V1 chemo-alone to V3 post-ipi) | Median +1.05% absolute increase in Treg frequency from V1 to V3 (statistically significant but biologically modest); CTLA-4+ Tregs unchanged | p=0.012 (Wilcoxon signed-rank) | — | exploratory-but-prespecified | pmc_full_text | Yi 2017 — ipi+chemo neoadj NSCLC. Full-text backfill 2026-04-23: median +1.05% Treg frequency increase post-ipi (p=0.012, statistically significant but tiny magnitude and opposite direction from depletion); CTLA-4+ Treg subset unchanged. |
| Neoadjuvant chemotherapy + ipilimumabNeoadjuvant chemotherapy + ipilimumab | Early-stage NSCLC (IB-IIIA) | 7 | Clin Cancer Res, 2017 | tumor | flow | — | null result null | Low | Moderate small-npbmc-only-generalizedno-multiplicity-correction | PMID PMCID DOI critique | 28951518 | window-of-opportunity | Per trial | FOXP3+ | frequency-of-lymphocytes | early-on-treatment | Surgical resection post-neoadj | Not measured — no pretreatment tumor samples available | Higher and more variable Treg levels than PBMCs in 7 post-resection tumors; no pre/post comparison | Cannot assess change — authors state 'in the absence of pre-treatment tumor samples, we are unable to adequately assess the effect of therapy on Treg frequencies within the tumor microenvironment' | not tested (paired analysis impossible) | — | exploratory-but-prespecified | pmc_full_text | Yi 2017 tumor compartment. Full-text backfill 2026-04-23: authors explicitly disclaim ability to assess Treg change in tumor (no pre-treatment biopsy). This row is 'not-assessed' correctly — retained as a documented limitation and because post-treatment tumor Treg data is still in-scope per schema. |
| Denileukin diftitox | Mycosis fungoides / Sézary syndrome (CTCL) | 15 | Cancer Immunol Immunother, 2018 | PBMC | flow | ↓ −29% | significant reduction depletion | Moderate | Moderate cd25-gating-confoundsmall-nno-multiplicity-correction | PMID PMCID DOI critique | 29204699 | single-arm-descriptive | Standard | CD4+CD25highFoxP3+ | frequency-of-CD4 | early-on-treatment | during treatment cycles | Not tabulated; CD4+FoxP3+ baseline count in blood per patient (n=15) | Median relative intra-patient change −29% in CD4+FoxP3+ (94% CI −83% to −20%) after one DD cycle | Median 29% reduction after one cycle (94% CI −83% to −20%); responders had significant 20-45% absolute number decrease after cycle 1; consecutive cycles produced sustained depletion | p=0.03 | Transient single-cycle effect with rebound between cycles; sustained with consecutive cycles | mechanism-targeted | pmc_full_text | Geskin 2018 — CTCL DD study. Full-text backfill 2026-04-23: median 29% reduction (94% CI −83%–−20%), p=0.03; responders achieved 20-45% decrease after cycle 1. Skin Treg decrease qualitatively shown in representative patient (unquantified). |
| Panobinostat | HIV-1 infection on suppressive cART (reservoir reactivation study) | 15 | mSphere, 2018 | PBMC | flow | ↑ +40% | increase null | Moderate | Low small-nno-multiplicity-correction | PMID PMCID DOI NCT critique | 29468194 | paired-pre-post | 20 mg PO 3× weekly x 8 weeks | CD4+CD25+FOXP3+ | frequency-of-CD4 | early-on-treatment | day 4 (peak) and day 28 (on-treatment) | baseline Treg proportion (value not numerically reported in abstract) | +40% at day 4; sustained elevation at day 28 | +40% Treg proportion at day 4 (p=0.003); similar elevation at day 28 (p=0.004) | p=0.003 (day 4); p=0.004 (day 28) | Treg elevation returned to baseline by 24-week follow-up post-treatment | pre-specified-endpoint | pmc_full_text | Brinkmann 2018 mSphere. PMC full text (PMC5812898). HIV reservoir-reactivation study — the pre-specified hypothesis was not Treg-depletion per se, but Treg PD was pre-specified. Panobinostat INCREASED Treg frequency and activation markers, opposite to the HDACi-driven Treg depletion paradigm in oncology. Important cross-indication counter-example: HDACi effects are context-dependent. Transient — returned to baseline 24 weeks post-treatment. |
| Ipilimumab or tremelimumab | Melanoma, prostate, bladder | 45 | Clin Cancer Res, 2019 | tumor | flow | ↑ sig. | increase null | High | Moderate foxp3-ihc-single-markersmall-nbaseline-imbalance | PMID PMCID DOI critique | 30054281 | paired-pre-post | Per trial | FOXP3+ | frequency-of-lymphocytes | early-on-treatment | Paired pre/post | Numeric density values shown only in Fig 2A plots without text quantification | Numeric density values shown only in Fig 2A plots without text quantification; direction is INCREASE across melanoma (ipi n=16 post vs 19 untreated; treme n=18 paired), no reduction in bladder (n=9) or prostate (n=16) | Both ipi (Mann-Whitney unpaired) and treme (Wilcoxon paired) significantly INCREASED FOXP3+ density in melanoma, p<0.05; 2 pre-treme patients with zero baseline FOXP3+ gained FOXP3+ infiltrate post-treme; bladder and prostate: no reduction | p<0.05 for melanoma cohorts (both ipi and treme); exact p-values not stated in text (figure-only) | — | mechanism-targeted | pmc_full_text | Sharma 2019 — foundational human null result. Full-text backfill 2026-04-23: both anti-CTLA-4 agents increased rather than depleted intratumoral FOXP3+ cells across melanoma, bladder, and prostate; exact density numbers in Fig 2A plots not textually quantified in paper. Consistent with Huang 2011 (21558401) baseline 35→167 cells/mm^2; both support the absence of Fc-mediated Treg depletion by non-Fc-enhanced anti-CTLA-4 in humans. Conflict pair with Ager 2026 (41759531): Ager shows Fc-enhanced anti-CTLA-4 DOES deplete intratumoral Tregs — the Fc engineering is the reconciling difference. |
| Bempegaldesleukin (NKTR-214) | Advanced/metastatic solid tumors | 28 | Cancer Discov, 2019 | PBMC | flow | ↑ qual. | ratio-shift only fraction shift | Low | Moderate abstract-onlyspin-abstract-vs-resultsindustry-sponsored | PMID DOI NCT critique | 30988166 | single-arm-descriptive | Dose-escalation | CD4+CD25+FoxP3+ | ratio-to-CD8 | early-on-treatment | Post-dose serial | — | — | CD8/Treg ratio increased; absolute Treg expansion but skewed toward effectors | reported | — | pre-specified-endpoint | pubmed_abstract | Bentebibel 2019 — bempeg first-in-human. Full-text backfill 2026-04-23: not in Europe PMC OA (inEPMC=N, subscription required). Abstract retains 'promoted immune cell increase with limited increase of Tregs' — consistent with the ratio-shift path. No numeric baseline/post Treg, CD8:Treg ratio, or fold change extractable from abstract. |
| Bempegaldesleukin (NKTR-214) + nivolumabNKTR-214 + nivolumab | Advanced solid tumors (melanoma, RCC, NSCLC, UC) | 38 | Cancer Discov, 2020 | PBMC | flow | ↑ qual. | ratio-shift only fraction shift | Low | Serious abstract-onlyspin-abstract-vs-resultsindustry-sponsored | PMID DOI NCT critique | 32439653 | single-arm-descriptive | Dose-escalation | CD4+CD25+FoxP3+ | ratio-to-CD8 | early-on-treatment | Post-dose serial | — | — | CD8/Treg ratio shift; Treg absolute expansion | reported | — | pre-specified-endpoint | pubmed_abstract | Diab 2020 PIVOT-02 — bempeg+nivo. Full-text backfill 2026-04-23: not in Europe PMC OA (inEPMC=N, subscription required). Abstract: 'increased infiltration, activation, and cytotoxicity of CD8+ T cells, without regulatory T-cell enhancement' — supports ratio-shift framing but no numeric values extractable. |
| Vorinostat + tamoxifen + pembrolizumabvorinostat (HDACi) + tamoxifen (endocrine) + pembrolizumab | ER+ advanced breast cancer, hormone-refractory | 21 | Nat Commun, 2020 | tumor | flow | ↓ −75.4% | significant reduction depletion | Moderate | Some concerns small-nresponder-subset-reportingindustry-sponsored | PMID PMCID DOI NCT critique | 32681091 | paired-pre-post | vorinostat + tamoxifen run-in, then add pembrolizumab | CD4+FoxP3+CTLA-4+ (activated Treg) | frequency-of-CD4 | early-on-treatment | post-run-in (pre-pembrolizumab) | 11.8% CD4+FoxP3+CTLA-4+ overall; 20.3% responders; 10.4% non-responders | 2.9% overall; 4.2% responders; 2.5% non-responders | overall 11.8% → 2.9% (−75%); responders 20.3% → 4.2% (−79%); non-responders 10.4% → 2.5% (−76%) | p=0.0067 overall; p=0.031 responders; p=0.034 non-responders | measured at end of run-in (~4 weeks) | mechanism-targeted | pmc_full_text | Terranova-Barberio 2020 Nat Commun. PMC full text (PMC7367885). Vorinostat HDACi-driven intratumoral Treg depletion replicated across responders and non-responders — notable because Treg depletion alone was not sufficient to predict benefit in this cohort. PBMC Tregs were not reported as depleted (tumor-specific effect). |
| Denileukin diftitox + IFNαIFNα | Advanced ovarian cancer | 12 | Clin Cancer Res, 2021 | PBMC | flow | ↓ sig. | significant reduction depletion | Low | Serious cd25-gating-confoundabstract-onlycase-report-n-of-fewspin-abstract-vs-results | PMID DOI critique | 33771857 | single-arm-descriptive | Per protocol | CD4+CD25highFoxP3+ | frequency-of-CD4 | early-on-treatment | during combination cycles | — | — | augmented depletion with IFNα | reported significant | — | mechanism-targeted | pubmed_abstract | Thibodeaux 2021 — DD+IFNα in ovarian cancer. Full-text backfill 2026-04-23: Clin Cancer Res article not in Europe PMC OA (inEPMC=N, subscription required). Abstract retains qualitative finding that DD depleted Tregs and IFNα augmented antitumor immunity; no numeric baseline/post Treg values extractable. |
| Low-dose decitabine | Immune thrombocytopenia (ITP) | 32 | Blood, 2021 | PBMC | flow | ↑ sig. | increase null | Moderate | Moderate no-multiplicity-correction | PMID PMCID DOI critique | 33876188 | paired-pre-post | 3.5 mg/m² IV x 3 days per 4-week cycle; 3 cycles total | CD4+CD25+FOXP3+ | frequency-of-CD4 | late | day 85 (post-3-cycle completion, ~12 weeks) | pretreatment Treg frequency (not numerically reported) | significantly increased Treg quantity and suppressive function | Treg quantity and function 'substantially improved' (p<0.05); no numeric % reported | p<0.05 | measured at day 85 post-initiation; durable through treatment window | pre-specified-endpoint | pmc_full_text | Han 2021 Blood (PMC8394906). Companion suppressive-function assay is paired with the count data — Tregs increased in BOTH quantity AND function (ex vivo CFSE-based suppression assay). This is opposite to Treg-depletion phenotype — an important null/counter-example for DNMTi effect on Tregs. Low-dose decitabine in autoimmunity tilts the balance TOWARD Treg dominance. |
| Entinostat + nivolumab ± ipilimumabentinostat (HDACi) + nivolumab ± ipilimumab | Advanced solid tumors (multiple histologies) | 14 | Clin Cancer Res, 2021 | tumor | flow | ↑ +119.7% | nonsignificant trend ratio only | Moderate | Moderate compartment-dissociationsmall-nno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 34135021 | paired-pre-post | entinostat 5 mg PO weekly (2-week run-in, then with ICI) | FOXP3+ cells (tumor IHC); CD8/FoxP3 ratio | ratio-to-CD8 | mid | Post-8-week combination (T2) vs baseline (T0) | median CD8/FoxP3 ratio 4.11 (baseline) | median CD8/FoxP3 ratio 9.03 at T2 (post-combination) | CD8:FoxP3 ratio increased 4.11 → 9.03 (2.2× shift in favor of CD8) | p=0.002 (Wilcoxon signed-rank, T0 vs T2) | measured at 8 weeks combination therapy | pre-specified-endpoint | pmc_full_text | Roussos Torres 2021 CCR (ETCTN-9844). PMC full text (PMC8563383). The ratio-shift is driven by both CD8 expansion and FoxP3 decrease; absolute Treg change not separately quantified. Entinostat monotherapy was insufficient — ICI was required for the shift. Note pct_change is for the CD8/FoxP3 ratio, not Tregs directly. |
| GWN323 (anti-GITR) ± spartalizumab (anti-PD-1)Spartalizumab | Advanced solid tumors and lymphomas | 53 | J Immunother Cancer, 2021 | PBMC | flow | ↓ qual. | nonsignificant trend depletion | Low | Moderate dose-mixed-analysisexploratory-endpointsingle-arm-no-controlindustry-sponsored | PMID PMCID DOI NCT critique | 34389618 | single-arm-descriptive | Dose-escalation | CD4+FoxP3+ | frequency-of-CD4 | early-on-treatment | On-treatment | Most patients had <1% FoxP3 at screening; 4 patients had >1% FoxP3 at baseline | 3 of 4 high-baseline patients had on-treatment FoxP3 decrease; non-dose-dependent | Inconsistent decreases limited to the 4/53 patients with detectable baseline Tregs; 3/4 of those decreased; non-dose-dependent across 10-1500 mg range | not tested; insufficient N | — | pre-specified-endpoint | pmc_full_text | Piha-Paul 2021 JITC GWN323 phase I. Full-text backfill 2026-04-23: authors explicitly note 'because most patients have no Foxp3 Treg cells in the tumor microenvironment at baseline, it may be impossible to test the hypothesis that GWN323 decreases Treg cells'; only 4 patients had assessable baseline Tregs; 3/4 decreased; non-dose-dependent. Classic anti-GITR human mixed result; underpowered for depletion claim. |
| Mogamulizumab | Sézary syndrome (CTCL) | 26 | Br J Dermatol, 2022 | PBMC | flow | ↓ sig. | significant reduction depletion | Moderate | Moderate abstract-onlyindustry-sponsored | PMID DOI critique | 35041763 | paired-pre-post | Standard | CD4+CD25+FOXP3+ activated Tregs | frequency-of-CD4 | early-on-treatment | Within first 4 weeks | — | — | drastic decrease in activated Tregs within first 4 weeks | reported significant | Long-term immune restoration noted | mechanism-targeted | pubmed_abstract | Roelens 2022 — long-term moga PD in Sézary syndrome. Full-text backfill 2026-04-23: Br J Dermatol article not in Europe PMC OA (inEPMC=N, subscription required). Abstract retains qualitative 'drastic decrease in activated Tregs within first 4 weeks'; 17/26 patients with early complete blood response correlated with higher baseline CCR4 expression. No numeric baseline/post values extractable. |
| Mogamulizumab | Sézary syndrome (CTCL) | 26 | Br J Dermatol, 2022 | skin | flow | mixed | significant reduction depletion | Moderate | Moderate abstract-onlyindustry-sponsored | PMID DOI critique | 35041763 | paired-pre-post | Standard | CD4+CD25+FOXP3+ | frequency-of-CD4 | late | Long-term follow-up | — | — | Long-term immune restoration; tumor heterogeneity reshaped | reported | Long-term restoration observed | mechanism-targeted | pubmed_abstract | Roelens 2022 skin compartment. Full-text backfill 2026-04-23: article not OA; abstract only describes 'long-term immune restoration' qualitatively for the skin compartment. No numeric skin Treg data extractable. |
| Idelalisib | Relapsed/refractory chronic lymphocytic leukemia | 9 | Br J Haematol, 2022 | PBMC | flow | ↓ sig. | significant reduction depletion | Low | Moderate very-small-nno-multiplicity-correction | PMID PMCID DOI NCT critique | 35170759 | paired-pre-post | 150 mg PO BID (per-label) | CD4+CD25+FOXP3+ | frequency-of-CD4 | early-on-treatment | visits 6-12 (roughly month 1-3 on treatment) | pre-treatment Treg frequency (not numerically reported) | uniformly decreased across all 9 patients | uniform decrease in Tregs with PI3Kδ inhibition (no numeric % in paper) | uniform across cohort; CD8:Treg ratio increase only statistically significant in toxicity subgroup (p<0.05) | — | mechanism-targeted | pmc_full_text | Gadi 2022 Br J Haematol. PMC full text (PMC9263710). Second trial is NCT01539291 (GS-US-312-0117). Small translational cohort (N=9) from the idelalisib phase III registration. Uniform Treg decrease reported qualitatively; no absolute numerics in full text. Toxicity-driving mechanism appears to be Th17 activation on top of Treg loss, not Treg loss alone. |
| Iberdomide (CC-220, cereblon modulator / Ikaros-Aiolos degrader) | Active systemic lupus erythematosus | 81 | Ann Rheum Dis, 2022 | PBMC | flow | ↑ +104.9% | increase null | Moderate | Some concerns no-multiplicity-correctionexploratory-endpointindustry-sponsoredauthor-coi-sponsor | PMID PMCID DOI NCT critique | 35477518 | randomized-controlled | 0.45 mg PO daily | TSDR demethylation (epigenetic Treg definition) | frequency-of-CD4 | late | week 24 vs placebo | baseline Treg frequency (not reported numerically in abstract/paper) | +104.9% vs placebo at 0.45 mg | +104.9% increase in Tregs at 0.45 mg vs placebo at week 24 | p<0.001 vs placebo | measured at week 24 on continued dosing | pre-specified-endpoint | pmc_full_text | Lipsky 2022 Ann Rheum Dis (PMC9279852). CELMoD iberdomide degrades Ikaros (IKZF1) and Aiolos (IKZF3) — NOT Helios (IKZF2). The consequence in SLE is IL-2-driven Treg EXPANSION, not destabilization. Critical conceptual boundary: Ikaros/Aiolos-degrading CELMoDs do not destabilize Tregs; an IKZF2-selective degrader would be required. This row anchors that distinction and corrects an initial assumption in the scope expansion. |
| TRX518 (anti-GITR) single agent or combo (gemcitabine / pembrolizumab / nivolumab)Gemcitabine OR pembrolizumab OR nivolumab | Advanced solid tumors | 109 | Clin Cancer Res, 2022 | PBMC | flow | mixed | nonsignificant trend depletion | Low | Moderate dose-mixed-analysissingle-arm-no-controlno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 35499569 | single-arm-descriptive | Dose-escalation | CD4+FoxP3+ | frequency-of-CD4 | early-on-treatment | Serial; combo-regimen-dependent kinetics | Baseline GITR+ Treg frequency: mean 41.82%, range 9.11-100% (Part C gem+TRX518 cohort); mean 36.63%, range 12.25-54.95% (Parts D+E anti-PD-1 combo cohort) | Monotherapy (Parts A+B, n=43): SD patients (n=11) had 'more substantial decreases in peripheral Tregs and eTregs' than PD patients; GITR+ Tregs consistently reduced in all patients, greater reduction in PD; gem combo: gem reduced Tregs days 1/8, TRX518 expanded on day 2 (cycle-level oscillation); anti-PD-1 combo: less consistent, CR patient had Treg INCREASE | Modest, inconsistent peripheral Treg reductions; kinetics varied by combo regimen; numeric fold-changes not text-quantified (figure-only) | p<0.05 indicated by asterisks in Fig 3A (unpaired t-test); exact values not stated | Combo-regimen-dependent: gem oscillation d1/8 (down) vs d2 (up with TRX518); anti-PD-1 less consistent | pre-specified-endpoint | pmc_full_text | Davar 2022 TRX518 Phase Ib. Full-text backfill 2026-04-23: modest inconsistent peripheral Treg reductions with significant combo-regimen dependence; baseline GITR+ frequency means provided (41.82% gem cohort, 36.63% anti-PD-1 cohort); ORR 3.2-12.5% across parts. Quantitative values mostly in figures without text numbers. |
| TRX518 (anti-GITR) single agent or comboGemcitabine OR pembrolizumab OR nivolumab | Advanced solid tumors | 20 | Clin Cancer Res, 2022 | tumor | flow | mixed | nonsignificant trend depletion | Low | Moderate dose-mixed-analysissingle-arm-no-controlno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 35499569 | paired-pre-post | Dose-escalation | FoxP3+ | frequency-of-lymphocytes | early-on-treatment | Pre and on-treatment biopsy | Per-tumor baseline; Fig 4A shows trajectories without tabulated density | Monotherapy (Parts A+B, n=13 evaluable): 7/13 had decreased intratumoral Tregs at C1D21; anti-PD-1 combo (Parts D+E, n=9 paired): 3 responders had 'profound intratumoral Treg reductions', 6 non-responders had increased or stable tumor Tregs; gem combo (Part C, n=21): no consistent change, clinical-benefit patients had INCREASED GITR+ Treg infiltration | Monotherapy: 7/13 (54%) decreased tumor Tregs; anti-PD-1 combo: 3/3 responders deep-depleters vs 6/6 non-responders not; gem combo: paradoxical increase in clinical benefiters | Paired t-test performed on Fig 4B; exact p not stated in text | C1D21 biopsy timepoint | pre-specified-endpoint | pmc_full_text | Davar 2022 TRX518 tumor. Full-text backfill 2026-04-23: 7/13 monotherapy patients depleted; 3/3 anti-PD-1 responders vs 0/6 non-responders (striking correlation); gem combo paradoxically enriched GITR+ Tregs in responders. |
| Decitabine + ipilimumabdecitabine (DNMTi) + ipilimumab (anti-CTLA-4) | Relapsed/refractory AML/MDS (post-allo-HCT and transplant-naïve) | 36 | Blood, 2023 | bone-marrow | flow | ↑ sig. | increase null | Moderate | Moderate small-nno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 36706355 | paired-pre-post | decitabine 20 mg/m² IV d1-5 lead-in; ipilimumab 3 or 10 mg/kg q3w | CD3+FOXP3+ (scRNA + multiplex IF) | frequency-of-CD3 | early-on-treatment | post-decitabine lead-in + post-ipilimumab infusion(s) | baseline marrow Treg density (not numerically reported) | increased CD3+FOXP3+ density post-ipilimumab | ipilimumab increased marrow-infiltrating Treg frequency (validated by scRNA-seq + mIF) | reported as qualitatively significant (no p-value cited in text) | — | mechanism-targeted | pmc_full_text | Penter 2023 Blood (PMC10122106) / Garcia 2023 Blood companion paper (PMID 36332187). This finding CONFLICTS with the canonical view that anti-CTLA-4 depletes tumor Tregs via ADCC. In the AML/MDS bone-marrow niche, ipilimumab (non-Fc-enhanced) appears to expand rather than deplete Tregs. Supports the Ager 2026 / Sharma 2019 Fc-engineering-reconciling-variable framework surfaced in the prior backfill run. Reinforces the rationale for Fc-enhanced anti-CTLA-4 (botensilimab, etc.) in Treg-rich niches. |
| Mogamulizumab (KW-0761) — anti-CCR4 Treg-targeted | CCR4-negative advanced solid tumors | 49 | PLoS One, 2023 | PBMC | flow | ↓ −90% | significant reduction depletion | High | Moderate industry-sponsoredauthor-coi-sponsor | PMID PMCID DOI critique | 37729184 | paired-pre-post | Per 1a/1b dose-escalation | CCR4+FOXP3+ eTreg | frequency-of-CD4 | early-on-treatment | 2 weeks post-first dose; sustained during treatment | Median 2.1% eTreg of CD4+ T cells (range 0.45-6.1%) | Median 0.20% eTreg of CD4+ (range 0.04-0.92%) at 4 weeks post-first dose | Median ~90% reduction (from 2.1% to 0.20%); eTreg depletion in all but 2 patients (where samples unavailable), 37 evaluable of 49 | reported in all patients (p-value not stated) | Sustained eTreg depletion during treatment, particularly durable in patients with clinical response | mechanism-targeted | pmc_full_text | Fujikawa 2023 PLoS One — integrated phase 1a/1b mogamulizumab. Full-text backfill 2026-04-23: median 2.1% → 0.20% at 4 weeks (~90% reduction); dose-independent (0.1-1.0 mg/kg). |
| Tiragolumab + atezolizumabatezolizumab (anti-PD-L1) | PD-L1-positive NSCLC | 16 | Nature, 2024 | PBMC | flow | ↓ qual. | nonsignificant trend depletion | Low | Moderate small-nexploratory-endpointindustry-sponsoredauthor-coi-sponsor | PMID PMCID DOI NCT critique | 38418879 | paired-pre-post | tiragolumab 600 mg q3w + atezolizumab 1200 mg q3w | FOXP3+ fraction of CD4+ T cells | frequency-of-CD4 | early-on-treatment | on-treatment (cycle not specified in text) | circulating Treg fraction of CD4+ (value not numerically reported) | decreased fraction of total CD4+ T cells | Treg fraction of total CD4 decreased on treatment (magnitude not quantified in manuscript) | reported as a group-level change; p-value not given | — | exploratory-but-prespecified | pmc_full_text | Guan 2024 Nature (CITYSCAPE NCT03563716 + phase 1b GO30103 translational cohort). PMC full text (PMC11139643). Peripheral Treg frequency decreased on-treatment but tumor Treg depletion not directly demonstrated in clinical samples — mouse CT26 data supported FcγR-dependent gene-signature shift only. Cleanest anti-TIGIT clinical Treg PD data available as of 2026-04-23; lacking numeric values. |
| Iberdomide + dexamethasonedexamethasone | Relapsed/refractory multiple myeloma | 197 | Cell Rep Med, 2024 | bone-marrow | flow | — | null result null | Moderate | Moderate exploratory-endpointno-multiplicity-correctionindustry-sponsoredauthor-coi-sponsor | PMID PMCID DOI NCT critique | 38776914 | single-arm-descriptive | iberdomide 0.3-1.6 mg PO + dex (CC-220-MM-001) | CD4+ regulatory phenotype (flow) | frequency-of-CD4 | baseline | screening bone marrow aspirate | 6.9% of CD4+ T cells Treg phenotype (all-comer median) | non-responders significantly higher baseline Treg vs responders (p<0.001) | baseline-only biomarker (no longitudinal depletion reported) | non-responder vs responder Treg: p<0.001 (baseline biomarker) | — | exploratory-but-prespecified | pmc_full_text | Amatangelo 2024 Cell Rep Med (PMC11228401). CC-220-MM-001 translational analysis. This row captures the BASELINE Treg biomarker finding, not a longitudinal depletion. Iberdomide in MM does NOT demonstrably deplete Tregs; baseline Treg elevation is a resistance marker. Confirms Lipsky 2022 SLE finding that iberdomide's mechanism is not Treg-depletion. |
| Bempegaldesleukin + nivolumabNKTR-214 + nivolumab | Melanoma / RCC / UC | 40 | NPJ Precis Oncol, 2024 | PBMC | flow | ↑ +800% | ratio-shift only fraction shift | Moderate | Moderate no-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 39025948 | paired-pre-post | Per trial | CD4+FOXP3+ | ratio-to-CD8 | early-on-treatment | Serial on-treatment | C1D1 baseline Treg frequency; per-patient data shown in Fig 4 | ~8-10x increase in absolute CD4+CD25+FoxP3+ Treg counts at C1D8 and C5D8 (bempeg+nivo arm); CD8+ T cells ~2x increase at same timepoints | Bempeg+nivo arm: Treg ~8-10x ABSOLUTE expansion but CD8/Treg ratio DECREASED at C1D8/C5D1/C5D8 vs baseline (Treg expansion outpaced CD8 2x expansion); nivo-monotherapy arm: ratios stable | p<0.00001 / p<0.0001 (multiple comparisons via asterisks in Fig 4; exact p not stated) | Serial sampling C1D1/C1D8/C5D1/C5D8 | pre-specified-endpoint | pmc_full_text | Gogas 2024 — PIVOT-02 biomarker re-analysis. Full-text backfill 2026-04-23: 8-10x Treg absolute expansion with bempeg+nivo (ratio shift NEGATIVE — Treg outpaced CD8); this actually argues AGAINST bempeg achieving a favorable Treg-relative effect. Row retained per user's explicit ratio-shift-path inclusion spec but directionality is unfavorable. |
| Botensilimab (AGEN1181) + balstilimab (anti-PD-1)Balstilimab | Advanced solid tumors (poorly ICI-responsive) | 12 | Cancer Discov, 2024 | tumor | flow | ↓ sig. | significant reduction depletion | Moderate | Moderate small-nsingle-arm-no-controlindustry-sponsoredauthor-coi-sponsor | PMID PMCID DOI NCT critique | 39083809 | paired-pre-post | Per dose-escalation | FOXP3+ | frequency-of-lymphocytes | early-on-treatment | On-treatment biopsy | Not quantified in main text; RNA-seq-based signal (Fig 5H) | Significant intratumoral Treg reduction by IHC and RNA-seq signature (Fig 5H); fold-change and p-value not stated in text | Human: significant intratumoral FOXP3+ reduction (IHC); numeric values not text-quantified. Mouse CT26: 'significant intratumoral FOXP3+ Treg reduction up to 10 days posttreatment' and increased CD8/Treg ratio (Fig 1D). Human PBMC mechanism: not attributed to depletion but to reduced TGFβ1 secretion (Suppl Fig S9B). | reported significant (intratumoral IHC); exact p not stated | Mouse: sustained up to 10 days post-treatment; human: single on-treatment biopsy | mechanism-targeted | pmc_full_text | Chand 2024 Cancer Discov — botensilimab translational. Full-text backfill 2026-04-23 (via Europe PMC PMCID PMC11609826): intratumoral FOXP3+ decrease in human IHC+RNA-seq but numerics not text-quantified; PBMC/serum Tregs unchanged (tumor-selective); preclinical mouse data more quantitative. Updated with PMCID. |
| Intraperitoneal denileukin diftitox (ONTAK) | Recurrent refractory ovarian cancer | 10 | Gynecol Oncol, 2024 | PBMC | flow | ↓ −73% | significant reduction depletion | Moderate | Moderate very-small-ndose-mixed-analysisno-multiplicity-correctionauthor-coi-sponsor | PMID PMCID DOI critique | 39362046 | single-arm-descriptive | Dose-escalation; MTD 15 µg/kg | CD4+CD25highFoxP3+ | frequency-of-CD4 | early-on-treatment | serial during dose escalation | Mean FoxP3 0.1726 ± 0.0442 (n=6) at baseline (pooled dose levels) | Mean FoxP3 0.0374 ± 0.0101 (n=5) at week 8 | Mean 73% reduction pooled; by dose: 5 µg/kg cohort 58.9% reduction (p=0.1500); 15 µg/kg cohort 83.2% reduction (p=0.0374); 5/9 patients achieved ≥25% reduction (secondary efficacy threshold) | p=0.0275 (pooled); p=0.0374 (15 µg/kg) | 8-week on-treatment measurement; recovery not reported | mechanism-targeted | pmc_full_text | Liao 2024 — IP route in ovarian. Full-text backfill 2026-04-23: pooled p=0.0275 with 73% reduction; dose-level breakdown shows only 15 µg/kg significant (p=0.0374). |
| Intraperitoneal denileukin diftitox (ONTAK) | Recurrent refractory ovarian cancer | 10 | Gynecol Oncol, 2024 | ascites | flow | ↓ −67% | nonsignificant trend depletion | Moderate | Moderate very-small-ndose-mixed-analysisno-multiplicity-correctionauthor-coi-sponsor | PMID PMCID DOI critique | 39362046 | single-arm-descriptive | Dose-escalation; MTD 15 µg/kg | CD4+CD25highFoxP3+ | frequency-of-CD4 | early-on-treatment | serial | Mean FoxP3 0.1855 ± 0.0945 (n=3) at baseline | Mean FoxP3 0.0597 ± 0.0304 (n=3) at week 8 | Mean 67% reduction in ascites FoxP3; 3 patients achieved ≥25% reduction (immunologic efficacy threshold) | p=0.2737 (n.s.; small sample) | 8-week on-treatment measurement | mechanism-targeted | pmc_full_text | Liao 2024 ascites compartment. Full-text backfill 2026-04-23: 67% mean reduction, n.s. (p=0.2737) — reclassified as 'partial' because direction is consistent with PBMC but underpowered (n=3 paired). |
| Nemvaleukin alfa (ALKS 4230) monotherapy | Advanced solid tumors (ARTISTRY-1) | 46 | J Immunother Cancer, 2024 | PBMC | flow | ↑ +100% | increase ratio only | Moderate | Moderate single-arm-no-controlno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 39567211 | single-arm-descriptive | 6 µg/kg/day IV days 1-5 q21d | CD4+CD25+FoxP3+ | frequency-of-CD4 | early-on-treatment | Serial cycles | C1D1 baseline; per-patient data only | Max fold change from baseline (FCBmax) for Tregs ~2x in both melanoma and RCC cohorts; CD8+ 2.53x, NK 6.52x for comparison (Part B monotherapy) | Tregs expanded ~2x (modest); CD8+ 2.53x; NK 6.52x — ratios favor effector expansion. Treg expansion limited to C1D5 only | reported qualitatively; no per-comparison p-values in main text | Transient Treg expansion at C1D5 only; effector expansion at D8 (cycle 1) and D22 (cycle 2) | pre-specified-endpoint | pmc_full_text | Vaishampayan 2024 ARTISTRY-1 monotherapy. Full-text backfill 2026-04-23: Treg FCBmax ~2x vs NK 6.52x / CD8 2.53x; nemva's IL-2R-βγ bias limited Treg expansion as designed. Kept via ratio-shift path. |
| Nemvaleukin alfa + pembrolizumabPembrolizumab | Advanced solid tumors (ARTISTRY-1 Part C) | 166 | J Immunother Cancer, 2024 | PBMC | flow | ↑ qual. | increase ratio only | Moderate | Moderate single-arm-no-controlno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 39567211 | single-arm-descriptive | 6 µg/kg/day IV days 1-5 q21d | CD4+CD25+FoxP3+ | frequency-of-CD4 | early-on-treatment | Serial cycles | C1D1 baseline; per-patient data only | Similar minimal Treg expansion pattern as monotherapy (~2x FCBmax) | Nemva+pembro: minimal Treg expansion; effector expansion preserved | reported qualitatively | — | pre-specified-endpoint | pmc_full_text | ARTISTRY-1 Part C combo. Full-text backfill 2026-04-23: combo cohort showed the same minimal Treg expansion pattern as monotherapy; CD8/NK ratios remained favorable. No separate numeric table for combo vs mono. |
| Denileukin diftitox (E7777 / I/ONTAK) | Treatment-refractory stage IV breast cancer | 15 | Vaccines (Basel), 2025 | PBMC | flow | ↓ qual. | nonsignificant trend depletion | Low | Moderate cd25-gating-confoundsmall-nindustry-sponsored | PMID PMCID DOI critique | 40006664 | single-arm-descriptive | Per protocol, up to six 21-day cycles | CD4+CD25+FOXP3+ | frequency-of-CD4 | early-on-treatment | post-cycle | Per-patient baseline; aggregate not tabulated | No significant difference between baseline and maximal observed Treg levels (overall p=0.10) | Overall depletion n.s. (p=0.10); 6/15 patients (40%) achieved ≥25% Treg reduction with mean reduction 56.0% ± 10.96% (SD) in this responder subset | p=0.10 (overall, n.s.) | Most reductions occurred after cycle 2; limited by rapid anti-DT IgG response (100% of 9 evaluable patients at week 6, p<0.005) | mechanism-targeted | pmc_full_text | Gwin 2025 — partial depletion in breast cancer. Full-text backfill 2026-04-23: overall p=0.10 (n.s.); responder subset (6/15, 40%) had 56.0% ± 10.96% mean reduction; 100% anti-DT IgG response by week 6 likely limited efficacy. |
| Mogamulizumab + nivolumab neoadjuvantNivolumab (3 doses) + mogamulizumab (4 doses) | Operable solid tumors (renal, lung, esophageal, oral SCC) | 16 | J Immunother Cancer, 2025 | tumor | flow | ↓ −86.7% | significant reduction depletion | Moderate | Low small-nsingle-arm-no-controlindustry-sponsored | PMID PMCID DOI critique | 40180420 | window-of-opportunity | Per protocol neoadjuvant | CCR4+FOXP3+ Tregs | frequency-of-CD4 | early-on-treatment | Preoperative post-neoadjuvant window | Per-tumor baseline CCR4+FoxP3+ density, not aggregated | Median −86.7% change in CCR4+FoxP3+ (range −94.8% to −52.7%) in all 16 patients; total FoxP3+ median change −11.1% (range −73.2% to +87.8%), decreased in 50% of patients | CCR4+ eTreg: median 86.7% reduction, depleted in 16/16; total FoxP3+ mixed response, 8/16 decreased | reported; p-values not published | Measured at surgery (preoperative neoadjuvant window) | mechanism-targeted | pmc_full_text | Jinushi 2025 JITC — neoadjuvant moga+nivo. Full-text backfill 2026-04-23: median 86.7% reduction in CCR4+FoxP3+ eTregs (100% depleted); total FoxP3+ more variable (median −11.1%, 50% decreased). |
| Mogamulizumab + recombinant human IL-15 (rhIL-15)Mogamulizumab + rhIL-15 | R/R T-cell malignancies (ATLL, MF/SS) | 6 | Blood Neoplasia, 2025 | PBMC | flow | — | ratio-shift only depletion | Low | Moderate very-small-nsurface-marker-gatingindustry-sponsored | PMID PMCID DOI critique | 40546724 | single-arm-descriptive | Dose-escalation | CD4+FOXP3+ (presumed) | frequency-of-CD4 | early-on-treatment | First cycle | — | — | NK expansion and tumor cell reduction reported; Treg-specific numeric not in abstract | not tested | — | mechanism-targeted | pmc_full_text | Gordon 2025 — mogamulizumab + rhIL-15 phase 1 in R/R T-cell malignancies. Full-text backfill 2026-04-23: PMC article reviewed (PMC12182836). Paper focuses on NK cell expansion and ADCC; no quantitative Treg baseline/post values, p-values, or fractional changes reported. Mechanism of mogamulizumab Treg depletion is assumed by reference to prior moga literature but NOT measured in this trial. Row retained because moga is mechanism-targeted and this is a mogamulizumab-containing regimen, but Treg PD is NOT a pre-specified endpoint here — borderline case. |
| Nemvaleukin alfa monotherapy | Advanced melanoma and RCC (post-ICI) | 74 | J Immunother Cancer, 2025 | PBMC | flow | ↑ +100% | increase ratio only | Moderate | Moderate single-arm-no-controlno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 40759440 | single-arm-descriptive | 6 µg/kg/day IV days 1-5 q21d | CD4+CD25+FoxP3+ | frequency-of-CD4 | early-on-treatment | Serial on-treatment | C1D1 baseline; per-patient only | Treg fold change ~2x (FCBmax at C1D5); CD8+/NK expansion larger at C1D8/C2D22 | Tregs ~2x FCBmax; effector cells (CD8+/NK) FCB larger at D8/D22; post-ICI melanoma and RCC both show this pattern | reported qualitatively | — | pre-specified-endpoint | pmc_full_text | Calvo 2025 ARTISTRY-1 Part B post-ICI cohort. Full-text backfill 2026-04-23: consistent ~2x Treg FCBmax limited to C1D5, contrasting with sustained effector expansion at D8/D22. |
| Nemvaleukin alfa (less-frequent IV dosing) | Advanced solid tumors | 30 | Oncologist, 2025 | PBMC | flow | ↑ qual. | increase ratio only | Low | Moderate single-arm-no-controlno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI critique | 40990800 | single-arm-descriptive | Q-variable IV schedules | CD4+CD25+FoxP3+ | frequency-of-CD4 | early-on-treatment | Serial across schedules | C1D1 baseline; per-patient only | Low-level transient non-dose-dependent Treg expansion; favorable effector:Treg ratios maintained | Minimal Treg expansion across schedules; figures only | reported qualitatively | — | pre-specified-endpoint | pmc_full_text | Piha-Paul 2025 ARTISTRY-3 less-frequent dosing. Full-text backfill 2026-04-23: 'low-level, transient, non-dose-dependent expansion of Tregs' with favorable NK:Treg and CD8:Treg ratios; Treg quantitative data in Fig 6 only. |
| BMS-986218 (Fc-enhanced anti-CTLA-4) + androgen deprivation therapy (ADT) neoadjuvantAndrogen deprivation therapy (ADT) | High-risk localized prostate cancer | 24 | Cell Rep Med, 2026 | tumor | flow | ↓ sig. | significant reduction depletion | Moderate | Some concerns small-nopen-labelno-multiplicity-correctionindustry-sponsored | PMID PMCID DOI NCT critique | 41759531 | randomized-controlled | Per trial | FOXP3+ (scRNA-seq + CyTOF) | frequency-of-CD4 | early-on-treatment | Baseline vs pre-surgery | Per-arm baseline TI-Treg frequency; density values not tabulated in text (figure panels only) | ADT+BMS-986218 arm significantly reduced TI-Treg frequency vs ADT alone (p=0.031); ADT alone arm had INCREASED TI-Tregs vs untreated (p=0.002) | Qualitative TI-Treg reduction in combo arm; residual TI-Tregs remained in all tumors (incomplete depletion); numeric density values in figure panels without text quantification | p=0.031 (ADT+BMS-986218 vs ADT alone); p=0.002 (ADT alone vs untreated, ADT expanded TI-Tregs) | Measured at radical prostatectomy (end of neoadjuvant window) | mechanism-targeted | pmc_full_text | Ager 2026 CRM — randomized phase 1 BMS-986218 (Fc-enhanced anti-CTLA-4) + ADT vs ADT alone. Full-text backfill 2026-04-23: TI-Treg reduction p=0.031 in combo arm; ADT alone expanded TI-Tregs (p=0.002); residual Tregs remained (partial depletion); CD16a+ macrophage correlation p=0.033. Numeric densities in figure panels not text-quantified. Conflict pair with Sharma 2019 (30054281): Sharma shows non-Fc-enhanced anti-CTLA-4 fails to deplete; Ager shows Fc-enhanced anti-CTLA-4 succeeds — reconciled by Fc-engineering difference. |