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Tumour-associated macrophages are immune cells that should eat cancer cells but are re-educated by the tumour to protect it instead. They are often the most abundant immune cell in a tumour.
Mostly M2-like, immunosuppressive, pro-angiogenic; recruited by CSF1 and CCL2; express PD-L1, SIRPα, TREM2. Targets: CSF1R (pexidartinib approved in TGCT; broadly disappointing in cancer), CD47/SIRPα (magrolimab failed), TREM2, CD40 agonists. Depleting M2 TAMs is also the rationale of the MERTK ADC RGX-019-MMAE.
In plain words · CD47 is the 'don't eat me' signal: it binds SIRP-alpha on macrophages to stop them engulfing the cell, and over 90% of AML blasts and large B-cell lymphoma cells display it. Blocking it should let macrophages eat tumour cells, but red cells carry CD47 too, so anaemia is built in, and the lead antibody magrolimab was dropped after failed trials.
Showing the target this term concerns: CD47.
This review is the standard map of the tumour microenvironment and the reason microenvironment-directed drugs, from anti-angiogenics to macrophage and fibroblast targeting agents, are developed alongside tumour-cell-directed ones.
Together with the 2002 Nature review this essay put inflammation on the cancer research agenda; the tumour-associated macrophage and IL-6 work that followed, and the aspirin prevention trials, trace back to it.
Shares A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06), Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03), Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04), Evorpacept.
Shares A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06), Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03), Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04), Evorpacept.
Shares A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC), A Trial of AK117 (Anti-CD47 Antibody) in Patients With Acute Myeloid Leukemia, A Study of AK117/AK112 in Metastatic Triple-Negative Breast Cancer, A Phase Ib/II Study of AK112 in Combination With AK117 in Advanced Malignant Tumors.
Shares CD14, Macrophage, Nutrient competition & metabolic immunosuppression, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals.
Shares Spevatamig, Peluntamig, A Study of Peluntamig (PT217) in Patients With Neuroendocrine Carcinomas Expressing DLL3 (the SKYBRIDGE Study), Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junct.
Shares Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS), Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia, Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been Treated, A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer.
Shares Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis, Macrophage, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals.
Shares Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients, Mitazalimab.