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The review that named and organised the field of checkpoint blockade: tumours switch off attacking T cells through brakes such as CTLA-4 and PD-1, and antibodies that release those brakes can produce lasting responses.
Written as the first PD-1 antibody results appeared, Pardoll's review explained how immune checkpoints, receptors that normally protect tissues from autoimmunity, are exploited by tumours, and why blocking them is a fundamentally different approach from vaccines or cytokines. It contrasted CTLA-4, which acts early in lymph nodes, with PD-1 and its ligand PD-L1, which act in the tumour itself, catalogued further checkpoints such as LAG-3 and TIM-3, and set out the questions that have shaped the decade since: biomarkers, combinations, and the autoimmune side effects that come with releasing the brakes.
This is the most cited map of the immunotherapy revolution and a good first read before the trials. Its predictions largely held: PD-1 pathway antibodies became the most widely used cancer drugs, PD-L1 testing entered practice, and LAG-3 blockade was approved in melanoma a decade later.
This is the standard overview of checkpoint immunotherapy for clinicians and scientists, tying together the trial results and the biology of response and resistance that guide today's combination trials.
This paper turned a hypothesis into a biomarker: tumour mutational burden is now measured by commercial panels and underpins the tissue-agnostic approval of pembrolizumab for TMB-high tumours. It also explains why smokers' lung cancers, long the hardest to treat, respond better to immunotherapy than never-smokers' cancers.
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.
Immunoediting is the conceptual backbone of modern immuno-oncology: it explains tumour heterogeneity, dormancy and late relapse, and why immunotherapy works by releasing pre-existing but suppressed immunity.
Shares Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade, Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer, Immune checkpoint, PD-L1.
Shares LAG-3, Immune surveillance and cancer immunoediting, Immune checkpoint, CTLA-4.
Shares Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade, Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma, CTLA-4, PD-1.
Shares Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma, Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer, CTLA-4, PD-1.
Shares Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer, PD-L1, PD-1, Immune checkpoint inhibitors.
Shares Schreiber, Old and Smyth 2011: cancer immunoediting, Immune surveillance and cancer immunoediting, Immune checkpoint inhibitors.
Shares Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer, PD-L1, PD-1, Immune checkpoint inhibitors.