The cancer-immunity cycle
Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.
Chen and Mellman's cycle: (1) dying tumour cells release neoantigens; (2) dendritic cells (BATF3+ cDC1) capture and cross-present them; (3) in lymph nodes, T cells are primed via TCR-MHC plus CD28-B7, with CTLA-4 as the brake; (4) effector T cells traffic via CXCL9/10-CXCR3; (5) infiltrate through vasculature and stroma; (6) recognise peptide-MHC-I; (7) kill via perforin/granzyme and IFN-γ, releasing more antigen. Each step has failure modes (low antigenicity, poor DC function, Treg-dominated priming, abnormal vessels, TGF-β stroma, MHC loss, PD-1 exhaustion) and matching drugs (radiation, STING agonists and vaccines for 1-2; anti-CTLA-4 for 3; anti-VEGF for 4-5; engagers and CAR-T bypass 6; anti-PD-1 for 7).
In one picture
A relay of seven runners. The race is only won if every baton is passed. Cancers usually drop only one or two batons, so the treatment that works is the one that fixes the step that actually failed, which is why the same drug cures one patient and does nothing for the next.
Diagram
top- Radiation, chemotherapy, oncolytic viruses and ADC payloads feed step 1 (immunogenic cell death)
- Vaccines and STING agonists load step 2; anti-CTLA-4 acts at step 3
- Anti-VEGF and stromal agents open steps 4-5
- Engagers, CAR-T and TCR-T replace step 6; anti-PD-1/PD-L1 releases step 7
Pages like this
not linked directly; found by shared links- PathwayExtrinsic apoptosis (death receptors)
Shares Immunogenic cell death, CD3, PD-1 / PD-L1 immune checkpoint & T-cell activation, T-cell engagers (bispecific) and the tags mechanism, mechanics-atlas.
- PathwayMismatch repair & microsatellite instability
Shares Antigen presentation & immune editing, Neoantigen, CTLA-4, Ipilimumab and the tags mechanism, mechanics-atlas.
- PathwayNutrient competition & metabolic immunosuppression
Shares Hot vs cold tumours, VEGF / VEGFR, PD-1, Pembrolizumab and the tags mechanism, mechanics-atlas.
- PathwayThe angiogenic switch & tumour vessels
Shares Ivonescimab, VEGF angiogenesis, VEGF / VEGFR, PD-1 and the tags mechanism, mechanics-atlas.
- PathwayMyeloid suppression: TAMs, MDSCs & don't-eat-me signals
Shares Cold tumours: immune deserts and exclusion, PD-L1, VEGF / VEGFR, Immune checkpoint inhibitors and the tags mechanism, mechanics-atlas.
- PathwayOncogenic viruses
Shares Antigen presentation & immune editing, PD-L1, PD-1, Pembrolizumab and the tags mechanism, mechanics-atlas.
- PathwayMutagenesis & mutational signatures
Shares Neoantigen, PD-1, Pembrolizumab and the tags mechanism, mechanics-atlas.
- PathwayFibroblast activation, desmoplasia & matrix stiffness
Shares Cold tumours: immune deserts and exclusion, Hot vs cold tumours, PD-1 and the tags mechanism, mechanics-atlas.