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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 Macrophage, Nutrient competition & metabolic immunosuppression, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals, Tumour microenvironment (TME).
Shares Magrolimab, CD47, Tumour microenvironment (TME).
Shares Macrophage, CD47.
Shares Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis.
Shares Magrolimab, CD47.
Shares Magrolimab, CD47.
Shares Myeloid suppression: TAMs, MDSCs & don't-eat-me signals, Tumour microenvironment (TME), PD-L1.
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.