{"entity":{"id":"myeloid-suppression-axis","kind":"pathway","name":"Myeloid suppression: TAMs, MDSCs & don't-eat-me signals","aka":[],"tldr":"Tumours recruit the body's clean-up cells (macrophages and immature myeloid cells) and re-train them as bodyguards. They switch off T cells, build vessels, and, when a therapeutic antibody flags a cancer cell for eating, are told 'don't eat me' by CD47 on its surface.","summary":"Tumour and stromal CSF1, CCL2, CXCL1/2/8, VEGF, G-CSF and IL-6 recruit monocytes and neutrophils and expand myeloid-derived suppressor cells (PMN- and M-MDSC) from the bone marrow. In the tumour, hypoxia, lactate, IL-4/IL-13 and IL-10 polarise macrophages toward an immunosuppressive TAM state (TREM2+, SPP1+, MRC1+) that secretes IL-10, TGF-β, arginase, PGE2, expresses PD-L1, SIRPα and VISTA, and promotes angiogenesis and metastasis (TMEM doorways). MDSCs suppress via arginase, iNOS, ROS and PD-L1. CD47 on tumour cells binds SIRPα to block phagocytosis; magrolimab (anti-CD47) failed in AML/MDS after promising phase 1 data, but CD47 remains pursued with bispecifics. CSF1R inhibition (pexidartinib, vimseltinib in tenosynovial giant cell tumour) depletes TAMs but compensatory MDSC influx blunts it in cancer; CD40 agonists and TLR agonists reprogram; CXCR2 and CCR2 blockade limit recruitment; STAT3 and PI3Kγ inhibitors reprogram. Trained immunity (BCG) and engineered CAR-macrophages try to conscript the same cells for the attack.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Tumor-associated_macrophage","links":[{"label":"DeNardo & Ruffell, Macrophages as regulators of tumour immunity and immunotherapy (Nat Rev Immunol 2019)","url":"https://doi.org/10.1038/s41577-019-0127-6"}],"tags":["mechanism","mechanics-atlas"],"related":[],"cancers":[],"sections":[],"technologies":["car-nk-macrophage","trained-innate-immunity","bcg-and-intravesical-therapy","checkpoint-inhibitor","monoclonal-antibody"],"targets":["csf1r","cd47","pdl1","vegf","vista","cxcr4"],"drugs":["pexidartinib","vimseltinib","magrolimab","bcg-intravesical"],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","nutrient-competition-tme","angiogenic-switch","myc","jak-stat"],"terms":["tumor-associated-macrophages","myeloid-derived-suppressor-cells","fc-effector","immune-exclusion"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression"],"keyPapers":["paper-denardo-nat-rev-immunol"],"journals":[],"dependsOn":[],"notes":[],"analogy":"A landlord who hires the neighbourhood's own bouncers, pays them in sugar and lactate, and hangs a sign on every door that reads 'don't touch, friend' (CD47). The police (T cells) are stopped at the door by the bouncers, and the cleaners (macrophages) read the sign and leave.","nodes":[{"id":"rec","label":"CSF1, CCL2, G-CSF, VEGF","x":12,"y":15,"targetId":"vegf"},{"id":"mono","label":"Monocytes, neutrophils","x":40,"y":15},{"id":"mdsc","label":"MDSCs (arginase, ROS)","x":40,"y":45},{"id":"tam","label":"TAMs (CSF1R, TREM2)","x":68,"y":15,"targetId":"csf1r"},{"id":"sup","label":"IL-10, TGF-β, PD-L1","x":68,"y":45,"targetId":"pdl1"},{"id":"tcell","label":"T cells suppressed","x":92,"y":62},{"id":"cd47","label":"CD47 → SIRPα 'don't eat'","x":40,"y":78,"targetId":"cd47"},{"id":"phag","label":"Phagocytosis (ADCP)","x":68,"y":82},{"id":"ang","label":"Angiogenesis, metastasis","x":92,"y":20},{"id":"cd40","label":"CD40 agonists, TLRs reprogram","x":12,"y":78}],"edges":[{"from":"rec","to":"mono","type":"activates"},{"from":"mono","to":"mdsc","type":"activates"},{"from":"mono","to":"tam","type":"activates"},{"from":"tam","to":"sup","type":"activates"},{"from":"mdsc","to":"sup","type":"activates"},{"from":"sup","to":"tcell","type":"inhibits"},{"from":"tam","to":"ang","type":"activates"},{"from":"cd47","to":"phag","type":"inhibits"},{"from":"tam","to":"phag","type":"activates"},{"from":"cd40","to":"sup","type":"inhibits"},{"from":"cd40","to":"phag","type":"activates"}],"interventions":["CSF1R inhibitors pexidartinib and vimseltinib (approved in tenosynovial giant cell tumour; disappointing in cancer)","CD47/SIRPα: magrolimab failed in AML/MDS; next-generation bispecifics and SIRPα-Fc in trials","CD40 agonists, TLR7/9 agonists, CXCR2/CCR2 blockade, PI3Kγ inhibitors as reprogrammers","CAR-macrophages, trained innate immunity (BCG) and antibody engineering for ADCP"]},"route":"/pathways/myeloid-suppression-axis/","neighbours":{"technology":[{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","route":"/technologies/car-nk-macrophage/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"bcg-and-intravesical-therapy","kind":"technology","name":"Intravesical therapy (BCG, chemotherapy, devices, gene and viral therapy)","route":"/technologies/bcg-and-intravesical-therapy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"trained-innate-immunity","kind":"technology","name":"Trained innate immunity","route":"/technologies/trained-innate-immunity/"}],"target":[{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"},{"id":"cd47","kind":"target","name":"CD47","route":"/targets/cd47/"},{"id":"csf1","kind":"target","name":"CSF1","route":"/targets/csf1/"},{"id":"csf1r","kind":"target","name":"CSF1R","route":"/targets/csf1r/"},{"id":"cxcr4","kind":"target","name":"CXCR4","route":"/targets/cxcr4/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"},{"id":"vista","kind":"target","name":"VISTA","route":"/targets/vista/"}],"drug":[{"id":"bcg-intravesical","kind":"drug","name":"Intravesical BCG","route":"/drugs/bcg-intravesical/"},{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"},{"id":"pexidartinib","kind":"drug","name":"Pexidartinib","route":"/drugs/pexidartinib/"},{"id":"vimseltinib","kind":"drug","name":"Vimseltinib","route":"/drugs/vimseltinib/"}],"pathway":[{"id":"immune-desert-exclusion","kind":"pathway","name":"Cold tumours: immune deserts and exclusion","route":"/pathways/immune-desert-exclusion/"},{"id":"complement-in-cancer","kind":"pathway","name":"Complement in cancer","route":"/pathways/complement-in-cancer/"},{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"},{"id":"angiogenic-switch","kind":"pathway","name":"The angiogenic switch & tumour vessels","route":"/pathways/angiogenic-switch/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"fc-effector","kind":"term","name":"Fc engineering / effector function","route":"/terms/fc-effector/"},{"id":"immune-exclusion","kind":"term","name":"Immune exclusion","route":"/terms/immune-exclusion/"},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/"},{"id":"myeloid-derived-suppressor-cells","kind":"term","name":"Myeloid-derived suppressor cells (MDSCs)","route":"/terms/myeloid-derived-suppressor-cells/"},{"id":"lymphoma-bio-hodgkin-microenvironment","kind":"term","name":"The Hodgkin microenvironment: when the cancer cell is the minority","route":"/terms/lymphoma-bio-hodgkin-microenvironment/"},{"id":"tumor-associated-macrophages","kind":"term","name":"Tumour-associated macrophages (TAMs)","route":"/terms/tumor-associated-macrophages/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}],"paper":[{"id":"paper-denardo-nat-rev-immunol","kind":"paper","name":"Macrophages as regulators of tumour immunity and immunotherapy","route":"/key-papers/paper-denardo-nat-rev-immunol/"},{"id":"paper-ho-pancreatic-tumour-microenvironment-review-nrco-2020","kind":"paper","name":"The tumour microenvironment in pancreatic cancer: clinical challenges and opportunities","route":"/key-papers/paper-ho-pancreatic-tumour-microenvironment-review-nrco-2020/"}],"cancer":[{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"}]}}