All
PBMC
tumor
TDLN
bone marrow
ascites
skin
other
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Trabectedin | Soft-tissue sarcoma (leiomyosarcoma, liposarcoma) | 5 | Cancer Cell, 2013 | tumor | IHC | ↓ qual. | significant reduction depletion | Low | not-amenable-to-standard-rob | PMID DOI critique | 23410977 | paired-pre-post | Standard trabectedin | — | absolute-count | early-on-treatment | Short on-treatment | — | — | Monocyte depletion (including TAMs) observed in treated patients | reported | — | mechanism-targeted | pubmed_abstract | Germano 2013 Cancer Cell — landmark paper establishing trabectedin's selective macrophage depletion mechanism. Includes small human/clinical sidecar (small N, ~5 paired biopsies per the preclinical+translational methodology). Low N for clinical row (borderline for N≥3 rule); retained as foundational. Full-text would confirm exact N and tissue-compartment magnitudes. |
| PF-04136309 (CCR2i) + FOLFIRINOXFOLFIRINOX (chemotherapy) | Borderline resectable / locally advanced pancreatic adenocarcinoma | 39 | Lancet Oncol, 2016 | tumor | flow | ↓ qual. | significant reduction depletion | Moderate | Serious | PMID PMCID DOI NCT critique | 27055731 | treated-vs-untreated | PF-04136309 500 mg BID oral + FOLFIRINOX | — | absolute-count | mid | 12 weeks of treatment, pre-surgical biopsies | — | — | Reduction in CCR2+ inflammatory monocytes and TAMs in blood and tumor (per paper's PD analysis) | reported | — | mechanism-targeted | pubmed_abstract | Nywening 2016 Lancet Oncol — landmark CCR2i+FOLFIRINOX pancreatic. Abstract safety/efficacy focused; full PMC text has monocyte/TAM PD data. Abstract-level extraction — numeric values require PMC full-text backfill. |
| AMG 820 (anti-CSF1R) | Advanced solid tumors | 25 | Clin Cancer Res, 2017 | skin | IHC | ↓ qual. | significant reduction depletion | Low | Moderate | PMID DOI critique | 28655795 | paired-pre-post | 0.5 mg/kg weekly or 1.5-20 mg/kg Q2W | — | absolute-count | mid | On-treatment biopsy | — | — | 'Reduced numbers of skin macrophages' plus pharmacodynamic serum CSF1 increase | reported | — | mechanism-targeted | pubmed_abstract | Papadopoulos 2017 Clin Cancer Res — AMG 820 first-in-human. Skin used as tissue-macrophage PD surrogate (biopsy of accessible skin, not tumor). Serum CSF1 increase as feedback. No tumor TAM data. |
| Intratumoral G100 (GLA-SE, TLR4 agonist) | Merkel cell carcinoma | 10 | Clin Cancer Res, 2019 | tumor | IHC | ↑ qual. | ratio-shift only repolarization | Low | Moderate | PMID PMCID DOI critique | 30093453 | paired-pre-post | G100 2-10 μg intratumoral weekly | — | polarization-marker-shift | early-on-treatment | Post-injection biopsies | — | — | Increased inflammation in injected tumors; CD8+ and CD4+ T-cell infiltration; activation of immune-related genes | reported | 2 patients recurrence-free at 44+/41+ months; 2 sustained PRs at 33+ months | mechanism-targeted | pubmed_abstract | Bhatia 2019 Clin Cancer Res — intratumoral G100 in Merkel cell carcinoma phase 1. TLR4 agonism intended to repolarize myeloid TME; abstract-level data are T-cell and gene-expression focused with no direct TAM CD68/CD163 quantification. depletion_success: not-assessed due to no direct macrophage readout. |
| Hu5F9-G4 (magrolimab) + rituximabRituximab (anti-CD20) | Relapsed/refractory DLBCL and follicular lymphoma | 22 | N Engl J Med, 2018 | tumor | phago | ↑ qual. | increase functional only | Low | Moderate | PMID PMCID DOI NCT critique | 30380386 | single-arm-descriptive | 5F9 1 mg/kg prime + 10-30 mg/kg QW maintenance + rituximab | — | phagocytosis-function | mid | On-treatment | — | — | ~100% CD47 receptor occupancy achieved at 30 mg/kg; phagocytosis mechanism inferred from preclinical + CD47 RO; no direct ex vivo phagocytosis assay quantified in abstract | reported | 91% ongoing responses at median follow-up 6.2-8.1 months | mechanism-targeted | pubmed_abstract | Advani 2018 NEJM — landmark CD47 blockade + rituximab in rituximab-refractory NHL. Mechanism is macrophage phagocytosis restoration, but direct ex vivo phagocytosis assay not quantified in abstract. Anemia is on-target phagocytosis signal (depletion of senescent RBCs). |
| Pexidartinib + paclitaxelPaclitaxel (chemotherapy) | Advanced solid tumors (breast cancer expansion) | 51 | Ther Adv Med Oncol, 2019 | PBMC | flow | ↓ −78.5% | significant reduction depletion | Moderate | Moderate | PMID PMCID DOI critique | 31258629 | paired-pre-post | Pexidartinib dose-escalation (600-2000 mg/d) + paclitaxel 80 mg/m2 | — | absolute-count | early-on-treatment | Cycle 1 | — | — | CD14dim/CD16+ monocyte levels decreased by 57-100%; plasma CSF-1 increased 1.6- to 53-fold | reported | — | mechanism-targeted | pubmed_abstract | Wesolowski 2019 Ther Adv Med Oncol — pexidartinib + paclitaxel phase 1b. Blood CSF1-dependent CD14dim/CD16+ monocytes pre-specified as CSF1R-depletion PD surrogate (D1 satisfied). Dose-dependent CSF1 feedback rise. No tumor TAM data in abstract. |
| PF-04136309 (CCR2i) + nab-paclitaxel/gemcitabineNab-paclitaxel + gemcitabine | Metastatic pancreatic ductal adenocarcinoma | 21 | Invest New Drugs, 2020 | PBMC | flow | mixed | null result null | Low | Serious | PMID DOI NCT critique | 31297636 | single-arm-descriptive | PF-04136309 500 mg BID + nab-pac/gem | — | absolute-count | early-on-treatment | Cycle 1-2 | — | — | No significant change in PD biomarkers; pulmonary toxicity led to study halt | n.s. | — | mechanism-targeted | pubmed_abstract | Noel 2020 Invest New Drugs — PF-04136309 + nab-pac/gem phase 1b. Null-result for CCR2-targeting PD in this chemo backbone; contrast with Nywening 2016 FOLFIRINOX success. Pulmonary toxicity and study halt are critical negative context. |
| LY3022855 (IMC-CS4, anti-CSF-1R) | Metastatic breast cancer (MBC) and castration-resistant prostate cancer (mCRPC) | 34 | Clin Cancer Res, 2020 | PBMC | flow | ↓ qual. | significant reduction depletion | Low | Serious | PMID DOI NCT critique | 32847933 | paired-pre-post | LY3022855 monotherapy, dose-escalation | — | absolute-count | early-on-treatment | Day 8 | — | — | CD14dim CD16bright monocytes decreased at day 8; circulating CSF-1 increased | reported | — | mechanism-targeted | pubmed_abstract | Autio 2020 Clin Cancer Res — LY3022855 monotherapy. Blood CD14dim CD16bright monocyte pre-specified PD (D1 satisfied). No tumor CD68 quantification in abstract. |
| Pexidartinib (PLX3397) | Relapsed/refractory pediatric leukemias and solid tumors | 16 | Clin Cancer Res, 2020 | PBMC | flow | ↓ qual. | significant reduction depletion | Low | Moderate | PMID PMCID DOI critique | 32943455 | single-arm-descriptive | 400, 600, 800 mg/m2 daily, 28-day cycles | — | absolute-count | early-on-treatment | Cycle 1 | — | — | Plasma MCSF rise; absolute monocyte count decrease | reported | One mesothelioma patient SD at C49+ | mechanism-targeted | pubmed_abstract | Boal 2020 Clin Cancer Res — pediatric pexidartinib phase 1. Blood monocyte count + MCSF as pre-specified CSF1R PD surrogate. |
| AMG 820 + pembrolizumabPembrolizumab (anti-PD-1) | Advanced solid tumors (pancreatic, CRC, NSCLC) | 116 | J Immunother Cancer, 2020 | PBMC | flow | ↓ qual. | significant reduction depletion | Moderate | Moderate | PMID PMCID DOI NCT critique | 33046621 | paired-pre-post | AMG 820 1100 mg or 1400 mg IV + pembrolizumab 200 mg Q3W | — | absolute-count | early-on-treatment | On-treatment | — | — | Reduction in CSF1-dependent CD16-expressing monocytes; accumulation of serum CSF1 and IL-34 | reported | — | mechanism-targeted | pubmed_abstract | Razak 2020 JITC — AMG 820 + pembrolizumab. PD target engagement (CD16+ monocyte reduction, CSF1/IL-34 feedback) achieved but not translated to clinical benefit — a PD/efficacy disconnect. |
| AMG 820 + pembrolizumabPembrolizumab (anti-PD-1) | Advanced solid tumors | 116 | J Immunother Cancer, 2020 | tumor | IHC | ↑ qual. | ratio-shift only repolarization | Moderate | Moderate | PMID PMCID DOI NCT critique | 33046621 | paired-pre-post | AMG 820 1100 mg + pembrolizumab 200 mg Q3W | — | other | mid | On-treatment biopsy | — | — | Increased PD-L1 expression and increased CD4 and CD8 cells in tumor biopsies | reported | — | mechanism-targeted | pubmed_abstract | Same trial as above (Razak 2020). Tumor compartment data is T-cell/PD-L1 centric; direct tumor CD68/CD163 TAM counts not reported. Row retained as paired PD endpoint from the same trial, with readout_type: other and depletion_success: not-assessed since no direct TAM quantification. |
| Emactuzumab + selicrelumab (CD40 agonist)Selicrelumab (CD40 agonist, RO7009789) | Advanced solid tumors | 37 | J Immunother Cancer, 2020 | PBMC | flow | ↓ qual. | significant reduction depletion | Moderate | Moderate | PMID PMCID DOI NCT critique | 33097612 | paired-pre-post | Emactuzumab 1000 mg + selicrelumab 16 mg Q3W | — | absolute-count | early-on-treatment | On-treatment | — | — | Reduction of CD14dim CD16bright monocytes; increase of Ki67+ CD8+ T cells; decrease of B cells | reported | — | mechanism-targeted | pubmed_abstract | Machiels 2020 JITC — emactuzumab + selicrelumab. Blood CD14dim CD16bright monocytes are pre-specified CSF1R-depletion PD surrogate (D1 satisfied). N=37 is estimate from reported 40.5% SD rate — actual N to verify in full text. |
| Emactuzumab (RG7155, anti-CSF1R) | Diffuse-type tenosynovial giant-cell tumor (dTGCT) | 36 | Eur J Cancer, 2020 | tumor | IHC | ↓ qual. | significant reduction depletion | Moderate | Moderate | PMID DOI NCT critique | 33161240 | paired-pre-post | 1000 mg IV every 2 weeks (optimal biological dose) | — | absolute-count | mid | On-treatment biopsy (post-cycle) | — | — | 'Substantial decrease' in CSF1R+ and CD68/CD163+ macrophages in on-treatment biopsies (36 patients with paired tissue) | reported | 2-year ORR 64%; responses durable during maintained dosing | mechanism-targeted | pubmed_abstract | Cassier 2020 EJC long-term update of emactuzumab in dTGCT. On-target macrophage depletion in synovial TGCT tissue (disease driven by CSF1/CSF1R axis). Abstract reports qualitative 'substantial decrease' in CSF1R+ and CD68/CD163+ macrophages; full-text would quantify. Landmark example of clinical TAM depletion with durable efficacy. |
| LY3022855 (anti-CSF-1R) | Advanced solid tumors | 52 | Invest New Drugs, 2021 | PBMC | flow | ↓ qual. | significant reduction depletion | Low | Moderate | PMID DOI NCT critique | 33624233 | paired-pre-post | Dose-escalation, 100 mg IV weekly (RP2D) | — | absolute-count | early-on-treatment | Multi-timepoint post-dose | — | — | TAMs and CD14dim CD16bright monocyte levels decreased with treatment; serum CSF-1 and IL-34 increased | reported | — | mechanism-targeted | pubmed_abstract | Dowlati 2021 Invest New Drugs — LY3022855 monotherapy phase 1. Abstract reports TAMs (unclear whether tumor or blood monocyte surrogate) decreased; PD engagement achieved without clinical efficacy. |
| LY3022855 + durvalumab or tremelimumabDurvalumab (anti-PD-L1) or tremelimumab (anti-CTLA-4) | Advanced solid tumors (NSCLC, ovarian cohorts) | 72 | Invest New Drugs, 2021 | PBMC | mixed | — | null result null | Low | Moderate | PMID DOI NCT critique | 33852104 | paired-pre-post | LY3022855 100 mg QW + durvalumab 750 mg Q2W | — | other | early-on-treatment | Cycle 1-2 | — | — | — | — | — | mechanism-targeted | pubmed_abstract | Falchook 2021 Invest New Drugs — LY3022855 + durvalumab/tremelimumab phase 1a/1b. Abstract is PK-focused with no explicit macrophage/monocyte PD data. Retained as companion row to Dowlati 2021 for intervention-class coverage; no specific TAM PD readout reported in abstract. |
| Bexmarilimab (FP-1305, anti-CLEVER-1) | Heavily pre-treated metastatic cancer | 30 | Clin Cancer Res, 2021 | PBMC | CyTOF | ↑ qual. | repolarized repolarization | High | Low | PMID PMCID DOI NCT critique | 34078651 | paired-pre-post | Dose-finding 0.3-10 mg/kg IV | — | polarization-marker-shift | early-on-treatment | Post-dose | — | — | Blood monocytes exhibited proinflammatory phenotypic switch; suppressed nuclear lipid signaling; impaired vacuolar ATPase-mediated endosomal acidification; peripheral T-cell activation | reported | — | mechanism-targeted | pubmed_abstract | Virtakoivu 2021 Clin Cancer Res — bexmarilimab Part I (n=30) of MATINS. Peripheral myeloid reprogramming signal captured via CyTOF (D1 + D7 satisfied). Multi-dimensional evidence supports repolarization. |
| Neoadjuvant selicrelumab (CD40 agonist) ± chemotherapyGemcitabine + nab-paclitaxel (in subset) | Resectable pancreatic ductal adenocarcinoma | 16 | Clin Cancer Res, 2021 | tumor | IHC | ↓ qual. | significant reduction ratio only | Moderate | Moderate | PMID PMCID DOI critique | 34112709 | single-arm-descriptive | Selicrelumab 16 mg IV, preoperative | — | ratio-M1-to-M2 | mid | Surgical resection ~2-4 weeks after dose | — | — | M2-like TAMs fewer in selicrelumab-treated tumors vs controls; tumor fibrosis reduced; intratumoral DCs more mature; T cells more active | reported | — | mechanism-targeted | pubmed_abstract | Byrne 2021 Clin Cancer Res — neoadjuvant selicrelumab in resectable PDAC window-of-opportunity. M2-like TAM reduction + DC maturation + T-cell activation is coherent repolarization/ratio-shift signal. Abstract qualitative; full text has numeric IHC data. |
| APX005M (sotigalimab) + cabiralizumab + nivolumabAPX005M (CD40 agonist) + nivolumab (anti-PD-1); cabiralizumab is anti-CSF1R | Advanced melanoma, NSCLC, RCC (anti-PD-1 resistant) | 26 | Clin Cancer Res, 2021 | PBMC | mixed | ↑ qual. | ratio-shift only repolarization | Moderate | Moderate | PMID PMCID DOI NCT critique | 34140403 | paired-pre-post | APX005M 0.3 mg/kg + cabiralizumab 4 mg/kg + nivolumab 240 mg Q2W | — | polarization-marker-shift | early-on-treatment | 4 hours post-infusion | — | — | Pro-inflammatory cytokine upregulation at 4h; CD40 and MCSF serum increase post-therapy | reported | — | mechanism-targeted | pubmed_abstract | Weiss 2021 Clin Cancer Res — dual macrophage-polarizing therapy (CD40 agonist + CSF1Ri) + nivo in ICI-resistant disease. PD engagement but poor clinical activity. Macrophage-polarization surrogates captured; no direct tumor TAM count readout in abstract. |
| Pexidartinib + sirolimusSirolimus (mTOR inhibitor) | Advanced sarcoma (including dedifferentiated/pleomorphic subtypes) | 18 | Clin Cancer Res, 2021 | tumor | IHC | ↓ qual. | significant reduction depletion | Low | Serious | PMID PMCID DOI NCT critique | 34321280 | paired-pre-post | Pexidartinib 1000 mg + sirolimus 2 mg daily (RP2D) | — | absolute-count | mid | On-treatment biopsy | — | — | 'Decreased proportion of activated M2 macrophages within tumor samples with treatment' | reported | — | mechanism-targeted | pubmed_abstract | Manji 2021 Clin Cancer Res — pexidartinib + sirolimus in sarcoma. Qualitative M2 macrophage reduction in tumor IHC; no absolute count values in abstract. |
| MIW815 (ADU-S100), intratumoral STING agonist | Advanced/metastatic solid tumors and lymphomas | 47 | Clin Cancer Res, 2022 | tumor | mixed | ↑ qual. | ratio-shift only repolarization | Moderate | Moderate | PMID DOI critique | 34716197 | paired-pre-post | Intratumoral 50-6400 μg weekly, 3-weeks-on/1-off | — | polarization-marker-shift | early-on-treatment | On-treatment biopsy | — | — | Evidence of systemic immune activation; inflammatory cytokines elevated; T-cell clonal expansion; tumor biopsy RNA expression changes | reported | — | mechanism-targeted | pubmed_abstract | Meric-Bernstam 2022 Clin Cancer Res — MIW815 (ADU-S100) intratumoral STING phase 1. STING-driven type-I IFN mechanism is intended to repolarize myeloid TME; abstract documents immune activation but not direct TAM count/polarization. Full-text required for specific myeloid PD. |
| Emactuzumab + atezolizumabAtezolizumab (anti-PD-L1) | Advanced solid tumors (ICB-naive UBC, melanoma; ICB-experienced NSCLC, UBC, melanoma) | 221 | J Immunother Cancer, 2022 | tumor | mIF | mixed | nonsignificant trend depletion | High | Moderate | PMID PMCID DOI NCT critique | 35577503 | paired-pre-post | Emactuzumab 1000 mg + atezolizumab 1200 mg Q3W | — | absolute-count | mid | On-treatment biopsy | — | — | TAM reduction observed but 'less TAM reduction in ICB-experienced compared with ICB-naïve patients'; persistence of a TAM subpopulation associated with CD8+ TIL increase | reported | — | mechanism-targeted | pubmed_abstract | Gomez-Roca 2022 JITC — emactuzumab + atezo phase 1b. Key observation: TAM reduction is less complete in ICB-experienced patients; a persistent TAM subpopulation correlates with CD8 TIL increase. Interpreted as repolarization signal alongside depletion. Abstract-level; quantitative magnitudes require full-text. |
| Axatilimab (SNDX-6352, anti-CSF1R) | Chronic graft-versus-host disease (cGVHD) | 40 | J Clin Oncol, 2023 | PBMC | flow | ↓ qual. | significant reduction depletion | Moderate | Moderate | PMID PMCID DOI NCT critique | 36459673 | single-arm-descriptive | 3 mg/kg IV Q4W (RP2D) | — | polarization-marker-shift | mid | Cycle 7 day 1 | — | — | ORR 50% at C7D1 (primary endpoint); ORR 82% across first 6 cycles | reported | Durable clinical responses; 58% significant symptom improvement per Lee Symptom Scale | mechanism-targeted | pubmed_abstract | Kitko 2023 JCO — axatilimab in cGVHD phase 1/2. Not a cancer indication but the best clinical proof of CSF1R-dependent macrophage-driven disease modulation in humans. Kept as in-scope because CSF1R macrophage ablation is the mechanistic target. No direct tumor TAM counts (not applicable); clinical-response magnitude used as PD surrogate. |
| Magrolimab + azacitidineAzacitidine | Higher-risk MDS | 95 | J Clin Oncol, 2023 | bone-marrow | phago | ↑ qual. | increase functional only | Low | Moderate | PMID PMCID DOI NCT critique | 36888930 | single-arm-descriptive | Magrolimab IV + aza standard | — | phagocytosis-function | mid | On-treatment | — | — | CR 33%, ORR 75%, mDOR 11.1 mo; mPFS 11.6 mo; TP53-mut CR 40% | reported | Median duration of CR 11.1 mo; mDOR 9.8 mo | mechanism-targeted | pubmed_abstract | Sallman 2023 JCO — magrolimab + aza in higher-risk MDS. CD47 blockade restores macrophage phagocytosis of MDS blasts (preclinical mechanism). Direct phagocytosis measurement not in abstract. Phase 3 ENHANCE (NCT04313881) subsequently failed (2024) — include for PD/efficacy context. |
| Eganelisib (IPI-549) ± nivolumabNivolumab (anti-PD-1) in combo cohort | Advanced solid tumors (melanoma, HNSCC, others) | 219 | Clin Cancer Res, 2023 | PBMC | mixed | — | null result null | Moderate | Moderate | PMID PMCID DOI NCT critique | 37000164 | paired-pre-post | Monotherapy 10-60 mg QD; combination 20-40 mg QD + nivolumab | — | polarization-marker-shift | early-on-treatment | Cycle 1-2 | — | — | PD-activity reported but abstract does not specify TAM/myeloid PD magnitude | — | — | mechanism-targeted | pubmed_abstract | Hong 2023 Clin Cancer Res — MARIO-1 eganelisib mono/combo phase 1. Abstract emphasizes safety and clinical activity; no quantitative TAM PD in abstract. MARIO-3 (O'Connell 2024) contains the TAM reprogramming data (captured below). |
| SEA-CD40 (non-fucosylated CD40 agonist) | Advanced solid tumors and lymphoma | 67 | J Immunother Cancer, 2023 | PBMC | mixed | ↑ qual. | nonsignificant trend repolarization | Moderate | Moderate | PMID PMCID DOI NCT critique | 37385724 | paired-pre-post | Dose-escalation, 10-30 μg/kg selected | — | polarization-marker-shift | early-on-treatment | 21-day cycles | — | — | Dose-dependent cytokine induction; activation and trafficking of innate and adaptive immune cells | reported | — | mechanism-targeted | pubmed_abstract | Coveler 2023 JITC — SEA-CD40 phase 1. Non-fucosylated Fc increases ADCP by FcγR-enhanced binding. PD data is blood cytokine/immune-activation focused; no direct tumor TAM quantification in abstract. |
| Bexmarilimab (FP-1305, anti-CLEVER-1) | Treatment-refractory advanced solid tumors | 138 | Cell Rep Med, 2023 | tumor | scRNA | ↑ qual. | repolarized repolarization | Moderate | Moderate | PMID PMCID DOI NCT critique | 38056464 | paired-pre-post | Dose-escalation 0.3-10 mg/kg IV | — | polarization-marker-shift | mid | On-treatment biopsies | — | — | Macrophage activation signatures increase on-treatment; disease control correlated with high pre-treatment intratumoral CLEVER-1 positivity and increasing on-treatment serum IFNγ | reported | — | mechanism-targeted | pubmed_abstract | Rannikko 2023 Cell Rep Med — MATINS first-in-human bexmarilimab. The MATINS trial (Part I+II). Bexmarilimab converts immunosuppressive TAMs to activated phenotype; direct phagocytosis/function changes documented. Part I (n=30) reported separately in Virtakoivu 2021 (below). |
| Neoadjuvant sotigalimab + chemoradiationChemoradiation | Locally advanced esophageal/gastroesophageal junction adenocarcinoma | 6 | Cancer Res Commun, 2024 | tumor | scRNA | ↑ qual. | repolarized repolarization | Moderate | Moderate | PMID PMCID DOI critique | 38181044 | paired-pre-post | Sotigalimab (APX005M) IV pre-CRT | — | scRNA-cluster-shift | early-on-treatment | Post initial sotigalimab dose, pre-CRT | — | — | Increased antigen presentation; altered myeloid metabolism; elevated T-cell activation/cytotoxicity; reduced TME Tregs | reported | — | mechanism-targeted | pubmed_abstract | Soto 2024 Cancer Res Commun — neoadjuvant sotigalimab + CRT in E/GEJ cancer. Deep TIME-profiling via scRNA-seq + CITEseq + MIBI. Myeloid metabolism + antigen-presentation shift is a high-quality repolarization signal on multi-marker evidence. |
| PY314 (anti-TREM2) + pembrolizumabPembrolizumab (anti-PD-1) | Advanced renal cell carcinoma (ICI-refractory) | 17 | Invest New Drugs, 2024 | tumor | IHC | — | null result null | Low | Moderate | PMID DOI NCT critique | 38372949 | single-arm-descriptive | PY314 + pembro | — | absolute-count | mid | RECIST | — | — | mPFS 1.4 mo; 1 PR, 4 SD | — | — | mechanism-targeted | pubmed_abstract | Beckermann 2024 Invest New Drugs — PY314 + pembro in CPI-refractory RCC. Abstract is PK/safety focused; no TAM PD magnitude. Clinical activity poor — TREM2 targeting does not overcome prior CPI resistance in RCC. |
| Metronomic trabectedin + low-dose cyclophosphamide (TARMIC)Low-dose cyclophosphamide | Advanced soft-tissue sarcoma | 28 | Mol Cancer, 2024 | tumor | IHC | ↓ qual. | nonsignificant trend depletion | Low | Serious | PMID PMCID DOI NCT critique | 38374062 | paired-pre-post | Metronomic trabectedin + low-dose cyclo | — | absolute-count | early-on-treatment | 4 weeks post-treatment | — | — | Decreased CD68+CD163+ macrophages in tumor biopsies of 9/28 patients (32%); CD8+ T-cell increase in 11/28 (39%); composite positive immune response in up to 57% | reported | — | mechanism-targeted | pubmed_abstract | Sun 2024 TARMIC Mol Cancer — metronomic trabectedin + cyclo in STS. 32% of patients show tumor CD68+CD163+ reduction — a partial-response signal. Compelling ratio-shift (9/28 TAM ↓ with 11/28 CD8 ↑) and PFS correlate. |
| Eganelisib + atezolizumab + nab-paclitaxelAtezolizumab (anti-PD-L1) + nab-paclitaxel (chemotherapy) | Metastatic triple-negative breast cancer (TNBC) | 12 | J Immunother Cancer, 2024 | tumor | scRNA | ↑ qual. | repolarized repolarization | Moderate | Moderate | PMID PMCID DOI NCT critique | 39214650 | paired-pre-post | Eganelisib 30 mg or 40 mg QD + atezo + nab-pac | — | scRNA-cluster-shift | mid | On-treatment biopsy | — | — | Gene signatures of TAM reprogramming, immune activation, and ECM reorganization detected; associated with longer PFS | reported | — | mechanism-targeted | pubmed_abstract | O'Connell 2024 JITC — MARIO-3 eganelisib + atezo + nab-pac TNBC. Paired biopsy multiplex IF + GeoMx spatial transcriptomics; TAM reprogramming (M2→M1) is the intended mechanism. Repolarization row; multi-marker evidence supports `succeeded`. N=12 refers to spatial transcriptomics paired-biopsy subset; 18 for PD-L1 IHC subset. |
| IO-108 (anti-LILRB2) ± pembrolizumabPembrolizumab (in combination arm) | Advanced solid tumors | 25 | J Immunother Cancer, 2024 | tumor | mixed | ↑ qual. | ratio-shift only repolarization | Moderate | Moderate | PMID PMCID DOI NCT critique | 39567210 | paired-pre-post | IO-108 dose-escalation Q3W | — | polarization-marker-shift | mid | On-treatment biopsy | — | — | PD gene expression changes reflecting increased tumor T-cell infiltration; baseline TIS predicts response | reported | One CR >2 years (Merkel cell carcinoma, monotherapy) | mechanism-targeted | pubmed_abstract | Taylor 2024 JITC — IO-108 anti-LILRB2 phase 1. Tumor transcriptomic PD (increased T-cell infiltration) is intended surrogate for myeloid reprogramming but direct macrophage cluster analysis not reported in abstract. |
| PY314 (anti-TREM2) | Platinum-resistant ovarian cancer | 16 | J Immunother Cancer, 2025 | tumor | IHC | ↓ qual. | ratio-shift only depletion | Moderate | Moderate | PMID PMCID DOI critique | 40081941 | single-arm-descriptive | PY314 dose-escalation Q3W | — | absolute-count | mid | RECIST assessment every 6 weeks | — | — | Mechanism: PY314 'depletes tumor-associated macrophages'; abstract does not quantify tumor CD68/TREM2 change | — | — | mechanism-targeted | pubmed_abstract | Yeku 2025 JITC — PY159 and PY314 (TREM1 agonist + TREM2 antagonist) parallel arms in platinum-resistant ovarian. Abstract emphasizes mechanism and clinical outcomes; direct tumor TAM quantification not in abstract. |
| PY159 (TREM1 agonist antibody) | Platinum-resistant ovarian cancer | 17 | J Immunother Cancer, 2025 | tumor | IHC | ↑ qual. | ratio-shift only repolarization | Moderate | Moderate | PMID PMCID DOI critique | 40081941 | single-arm-descriptive | PY159 dose-escalation Q3W | — | polarization-marker-shift | mid | RECIST every 6 weeks | — | — | Mechanism: PY159 'reprograms immunosuppressive intratumoral myeloid cells'; abstract does not quantify | — | — | mechanism-targeted | pubmed_abstract | Yeku 2025 JITC PY159 arm. Paired with PY314 row above. Classified as other-repolarizing since PY159 is a myeloid-reprogramming agonist not fitting the 12 canonical families exactly. |
| BMS-813160 (CCR2/5 dual antagonist) + nivolumab + gemcitabine + nab-paclitaxelNivolumab + gemcitabine + nab-paclitaxel | Borderline resectable / locally advanced pancreatic cancer | 32 | Clin Cancer Res, 2025 | tumor | IHC | ↓ qual. | significant reduction depletion | Moderate | Moderate | PMID PMCID DOI NCT critique | 40125795 | randomized-controlled | BMS-813160 + nivo + GnP neoadjuvant, 4 cycles | — | absolute-count | mid | After 4 cycles neoadjuvant | — | — | Intratumoral monocytes and macrophages decreased; T-cell proliferation and effector genes enhanced | reported | — | mechanism-targeted | pubmed_abstract | Grierson 2025 Clin Cancer Res — BMS-813160 + nivo + GnP neoadjuvant PDAC. Randomized-controlled design with GnP-alone control (N=8). Clear intratumoral TAM reduction + T-cell activation + clinical activity. |
| Magrolimab + azacitidine + venetoclaxAzacitidine + venetoclax | AML (first-line and R/R) | 106 | Clin Cancer Res, 2025 | bone-marrow | phago | ↑ qual. | increase functional only | Low | Moderate | PMID PMCID DOI critique | 40198272 | single-arm-descriptive | Magrolimab + aza + ven standard | — | phagocytosis-function | mid | On-treatment | — | — | 1L CRc 63% (49% TP53-mut, 90% TP53 wt); R/R CRc 29% | reported | 1L mEFS 6.6 mo, mOS 9.8 mo | mechanism-targeted | pubmed_abstract | Daver 2025 Clin Cancer Res — aza+ven+magrolimab in AML. CD47-phagocytosis mechanism; no direct ex vivo phagocytosis in abstract. Context: broader magrolimab program halted after sepsis/anemia signals. |
| Bexmarilimab + azacitidineAzacitidine | MDS and R/R AML | 33 | Lancet Haematol, 2025 | bone-marrow | mixed | — | ratio-shift only repolarization | Low | Moderate | PMID DOI NCT critique | 40449509 | single-arm-descriptive | Bexmarilimab 1, 3, or 6 mg/kg IV weekly + aza standard | — | polarization-marker-shift | mid | Cycle 1-cycle 6 | — | — | ORR 45% (15/33); MTD not reached | reported | Median follow-up 6.2 months | mechanism-targeted | pubmed_abstract | Kontro 2025 Lancet Haematol — bexmarilimab + aza in MDS/AML phase 1. Marrow-macrophage reprogramming is the intended mechanism but direct marrow macrophage PD data not in abstract. Included for intervention coverage and the first hematologic CLEVER-1 trial. |
| Evorpacept (ALX148) + lenalidomide + rituximabLenalidomide + rituximab | Relapsed/refractory B-cell NHL (mostly indolent) | 20 | Clin Cancer Res, 2025 | tumor | mIF | ↑ qual. | repolarized expansion + repol | Low | Moderate | PMID PMCID DOI NCT critique | 40729376 | paired-pre-post | Evorpacept 30 or 60 mg/kg + lenalidomide 20 mg + rituximab 375 mg/m2 | — | polarization-marker-shift | early-on-treatment | End of cycle 1 | — | — | Significant increase in T cells and macrophages; anti-tumoral macrophage pathways upregulated | reported | Median follow-up 28 mo; 2-yr PFS 69% | mechanism-targeted | pubmed_abstract | Strati 2025 Clin Cancer Res — evorpacept + len + rituximab in R/R B-NHL. Rare example of intratumoral macrophage expansion toward anti-tumoral (M1-like) polarization. Assigned expansion-with-repolarization mechanism. |