# The cancer-immunity cycle

Source: https://onco.cc/pathways/cancer-immunity-cycle/  
OnCo record `cancer-immunity-cycle` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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).

## Fields

- Kind: Pathway
- Last checked: 2026-09-09
- Tags: mechanism; mechanics-atlas
- Analogy: 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.
- Interventions: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cancer_immunology
- Chen & Mellman, Oncology meets immunology: the cancer-immunity cycle (Immunity 2013): https://doi.org/10.1016/j.immuni.2013.07.012
- Chen & Mellman, Elements of cancer immunity and the cancer-immune set point (Nature 2017): https://doi.org/10.1038/nature21349

## Connected records

- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [cGAS-STING innate sensing](https://onco.cc/pathways/cgas-sting/), [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [T-cell exhaustion](https://onco.cc/pathways/t-cell-exhaustion/), [Theories of cancer: how the ideas connect](https://onco.cc/pathways/theories-of-cancer/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Immune surveillance and cancer immunoediting](https://onco.cc/terms/immune-surveillance-immunoediting/), [Immunogenic cell death](https://onco.cc/terms/immunogenic-cell-death/), [Neoantigen](https://onco.cc/terms/neoantigen/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [STING & innate immune agonists](https://onco.cc/technologies/sting-agonist/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [Adenosine A2A receptor (ADORA2A)](https://onco.cc/targets/adora2a/), [CD112 (nectin-2)](https://onco.cc/targets/nectin2/), [CD137 (4-1BB, TNFRSF9)](https://onco.cc/targets/cd137/), [CD155 (PVR)](https://onco.cc/targets/pvr/), [CD24](https://onco.cc/targets/cd24/), [CD27](https://onco.cc/targets/cd27/), [CD28](https://onco.cc/targets/cd28/), [CD3](https://onco.cc/targets/cd3/), [CD39 (ENTPD1)](https://onco.cc/targets/entpd1/), [CD40](https://onco.cc/targets/cd40/), [CD80 (B7-1)](https://onco.cc/targets/cd80/), [CD86 (B7-2)](https://onco.cc/targets/cd86/), [CD96](https://onco.cc/targets/cd96/), [CTLA-4](https://onco.cc/targets/ctla4/), [GITR (TNFRSF18)](https://onco.cc/targets/tnfrsf18/), [HHLA2 (B7-H7)](https://onco.cc/targets/hhla2/), [HLA-A](https://onco.cc/targets/hla-a/), [HLA-E](https://onco.cc/targets/hla-e/), [IDO1](https://onco.cc/targets/ido1/), [Interleukin-10 (IL10)](https://onco.cc/targets/il10/), [KIR2DL1 (inhibitory KIR)](https://onco.cc/targets/kir2dl1/), [LILRB1 (ILT2)](https://onco.cc/targets/lilrb1/), [LILRB2 (ILT4)](https://onco.cc/targets/lilrb2/), [NKG2A (KLRC1)](https://onco.cc/targets/klrc1/), [OX40 (TNFRSF4)](https://onco.cc/targets/tnfrsf4/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [PVRIG (CD112R)](https://onco.cc/targets/pvrig/), [Siglec-10](https://onco.cc/targets/siglec10/), [TDO2](https://onco.cc/targets/tdo2/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Ivonescimab](https://onco.cc/drugs/ivonescimab/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- key papers: [Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels](https://onco.cc/key-papers/paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022/), [Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042](https://onco.cc/key-papers/paper-keynote-042-tmb-mutations-ann-oncol-2023/), [Associations of tissue tumour mutational burden and mutational status with clinical outcomes with pembrolizumab plus chemotherapy versus chemotherapy for metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-keynote-189-407-tmb-jtocrr-2023/), [Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial](https://onco.cc/key-papers/paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024/), [Challenges and opportunities for pancreatic cancer immunotherapy](https://onco.cc/key-papers/paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020/), [Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas](https://onco.cc/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/), [Elements of cancer immunity and the cancer-immune set point](https://onco.cc/key-papers/paper-chen-nature/), [Galon 2006: the type, density and location of immune cells in colorectal tumours predict outcome](https://onco.cc/key-papers/paper-galon-immune-contexture-colorectal-science-2006/), [Genomic correlates of immune-cell infiltrates in colorectal carcinoma](https://onco.cc/key-papers/paper-giannakis-genomic-correlates-immune-colorectal-cell-rep-2016/), [Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer](https://onco.cc/key-papers/paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017/), [Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability](https://onco.cc/key-papers/paper-mlecnik-immunoscore-msi-colorectal-immunity-2016/), [International validation of the consensus Immunoscore for the classification of colon cancer](https://onco.cc/key-papers/paper-pages-immunoscore-international-validation-lancet-2018/), [Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ](https://onco.cc/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/), [Molecular determinants of response to anti-PD-1 and anti-PD-L1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing](https://onco.cc/key-papers/paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018/), [MSH2 loss in primary prostate cancer](https://onco.cc/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/), [NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients](https://onco.cc/key-papers/paper-niche-2-nejm-2024/), [Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden](https://onco.cc/key-papers/paper-checkmate-227-n-engl-j-med-2018/), [Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities](https://onco.cc/key-papers/paper-gay-sclc-subtypes-inflamed-cancer-cell-2021/), [Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade](https://onco.cc/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/), [Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer](https://onco.cc/key-papers/paper-rizvi-mutational-landscape-pd1-science-2015/), [Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer](https://onco.cc/key-papers/paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)

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