{"entity":{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nrc3239"}],"tags":[],"related":["paper-hodi-ipilimumab-melanoma-nejm-2010","paper-topalian-anti-pd1-nejm-2012"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["ctla4","pd1","pdl1","lag3","tim3"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["immune-checkpoint","irae"],"trials":[],"people":["drew-pardoll"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2012,"doi":"10.1038/nrc3239","authors":"Pardoll DM.","paperType":"review","findings":["Immune checkpoints are inhibitory receptors on T cells that tumours co-opt; CTLA-4 acts mainly during T cell priming and PD-1 during the effector phase in tissues.","PD-L1 expression by tumour cells offers a mechanism-based biomarker and a rationale for anti-PD-1 and anti-PD-L1 antibodies.","Multiple additional checkpoints (LAG-3, TIM-3, BTLA, adenosine and others) offer combination targets."],"whatItMeans":"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.","caveats":["A review written before most phase 3 evidence existed.","Biomarkers for checkpoint blockade remain imperfect despite the mechanistic case for PD-L1."],"changedPractice":false},"route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/","neighbours":{"paper":[{"id":"paper-chen-mellman-cancer-immunity-cycle-immunity-2013","kind":"paper","name":"Chen and Mellman 2013: the cancer-immunity cycle","route":"/key-papers/paper-chen-mellman-cancer-immunity-cycle-immunity-2013/"},{"id":"paper-hodi-ipilimumab-melanoma-nejm-2010","kind":"paper","name":"Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma","route":"/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/"},{"id":"paper-ribas-wolchok-checkpoint-blockade-science-2018","kind":"paper","name":"Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade","route":"/key-papers/paper-ribas-wolchok-checkpoint-blockade-science-2018/"},{"id":"paper-rizvi-mutational-landscape-pd1-science-2015","kind":"paper","name":"Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer","route":"/key-papers/paper-rizvi-mutational-landscape-pd1-science-2015/"},{"id":"paper-schreiber-cancer-immunoediting-science-2011","kind":"paper","name":"Schreiber, Old and Smyth 2011: cancer immunoediting","route":"/key-papers/paper-schreiber-cancer-immunoediting-science-2011/"},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","route":"/key-papers/paper-topalian-anti-pd1-nejm-2012/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"lag3","kind":"target","name":"LAG-3","route":"/targets/lag3/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"tim3","kind":"target","name":"TIM-3","route":"/targets/tim3/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"term":[{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"immune-surveillance-immunoediting","kind":"term","name":"Immune surveillance and cancer immunoediting","route":"/terms/immune-surveillance-immunoediting/"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"}],"person":[{"id":"drew-pardoll","kind":"person","name":"Drew M. Pardoll","route":"/people/drew-pardoll/"}]}}