# Chen and Mellman 2013: the cancer-immunity cycle

Source: https://onco.cc/key-papers/paper-chen-mellman-cancer-immunity-cycle-immunity-2013/  
OnCo record `paper-chen-mellman-cancer-immunity-cycle-immunity-2013` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The seven-step diagram of how the immune system should destroy a cancer, from releasing tumour antigens to killing tumour cells, and the idea that each patient's cancer breaks the cycle at a different step, which tells you which immunotherapies to combine.

## Summary

Chen and Mellman at Genentech laid out the cancer-immunity cycle: release of cancer cell antigens, antigen presentation by dendritic cells, priming and activation of T cells, trafficking to the tumour, infiltration, recognition of cancer cells and killing, which releases more antigens. They argued that effective immunity requires every step to work, that tumours block different steps in different patients, and that therapies should be matched to the rate-limiting step, with PD-L1 and PD-1 blockade acting at the final killing step. They introduced the term immunostat for the factors that set the balance.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Immunity
- Year: 2013
- DOI: 10.1016/j.immuni.2013.07.012
- Authors: Chen DS, Mellman I.
- Findings: Anti-cancer immunity proceeds through seven steps from antigen release to tumour cell killing, each of which can fail.; Different tumours and patients are limited at different steps, so no single immunotherapy will work for all.; Checkpoint blockade acts at the recognition and killing step; other therapies target priming, trafficking or infiltration.
- What it means: The cycle is the most used framework for designing immunotherapy combinations, from vaccines and radiotherapy that release antigens to drugs that recruit T cells into cold tumours. Most trial rationales in immuno-oncology cite it.
- Caveats: A conceptual review; the steps are idealised and the rate-limiting step is hard to measure in practice.; Written by authors at a company developing a PD-L1 antibody.

## Sources

- Full text (DOI): https://doi.org/10.1016/j.immuni.2013.07.012

## Connected records

- key papers: [Binnewies 2018: understanding the tumour immune microenvironment for effective therapy](https://onco.cc/key-papers/paper-binnewies-tumor-immune-microenvironment-natmed-2018/), [Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy](https://onco.cc/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Immune surveillance and cancer immunoediting](https://onco.cc/terms/immune-surveillance-immunoediting/), [Immune system](https://onco.cc/terms/immune-system/), [Neoantigen](https://onco.cc/terms/neoantigen/)

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