Chen and Mellman 2013: the cancer-immunity cycle
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.
Overview
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.
- 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.
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.
- 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.
Similar pages
not linked directly; found by shared links- Key paperThorsson 2018: the immune landscape of cancer across 10,000 tumours
Shares Binnewies 2018: understanding the tumour immune microenvironment for effective therapy, Immune system, Neoantigen, Immune checkpoint inhibitors.
- Key paperRizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Neoantigen, PD-1, Immune checkpoint inhibitors.
- Key paperSchreiber, Old and Smyth 2011: cancer immunoediting
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Immune system, PD-L1, Immune checkpoint inhibitors.
- CompanyOnc.AI
Shares PD-L1, PD-1, Immune checkpoint inhibitors.
- PersonGordon J. Freeman
Shares PD-L1, PD-1, Immune checkpoint inhibitors.
- PersonLieping Chen
Shares PD-L1, PD-1, Immune checkpoint inhibitors.
- TermHallmark: avoiding immune destruction
Shares Immune system, Hot vs cold tumours, PD-L1, PD-1.
- PersonDrew M. Pardoll
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, PD-L1, PD-1, Immune checkpoint inhibitors.