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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.
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.
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.
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