{"entity":{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","aka":["immune checkpoints","checkpoint protein","checkpoint proteins","checkpoint blockade","immune checkpoint blockade","checkpoint inhibition","checkpoint inhibitor","checkpoint inhibitors","immune checkpoint inhibitor","immune checkpoint inhibitors","ICI","ICIs","PD-1 blockade","PD-1/PD-L1","anti-PD-1","anti-PD-L1","anti-CTLA-4","PD-(L)1"],"tldr":"Brakes on the immune system that stop T cells attacking healthy tissue. Tumours pull these brakes to protect themselves; checkpoint inhibitor drugs release them so T cells can attack the cancer.","summary":"PD-1 on a T cell, when it meets PD-L1 on another cell, tells the T cell to stand down; CTLA-4 acts earlier, when T cells are first activated. Tumours coat themselves in PD-L1 and exploit this, and antibodies that block PD-1 (pembrolizumab, nivolumab), PD-L1 (atezolizumab, durvalumab) or CTLA-4 (ipilimumab) restore the attack, producing durable remissions in melanoma, lung, kidney, bladder and many other cancers since 2011. The price is autoimmune side effects when the brakes come off everywhere, and only a minority of patients respond, which drives the search for newer checkpoints (LAG-3, TIGIT) and combinations. The 'checkpoint' in 'cell-cycle checkpoint' is an unrelated concept.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Immune_checkpoint","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Immune_checkpoint"}],"tags":[],"related":["checkpoint","t-cell","immune-system","immunotherapy-term","irae","cold-vs-hot","cps","avoiding-immune-destruction"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1","ctla4","lag3","tigit"],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},"route":"/terms/immune-checkpoint/","neighbours":{"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"avoiding-immune-destruction","kind":"term","name":"Hallmark: avoiding immune destruction","route":"/terms/avoiding-immune-destruction/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"immune-system","kind":"term","name":"Immune system","route":"/terms/immune-system/"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"immunotherapy-term","kind":"term","name":"Immunotherapy","route":"/terms/immunotherapy-term/"},{"id":"t-cell","kind":"term","name":"T cell","route":"/terms/t-cell/"}],"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":"tigit","kind":"target","name":"TIGIT","route":"/targets/tigit/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"paper":[{"id":"paper-felip-impower010-adjuvant-atezolizumab-lancet-2021","kind":"paper","name":"Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)","route":"/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/"},{"id":"paper-adriatic-nejm-2024","kind":"paper","name":"ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer","route":"/key-papers/paper-adriatic-nejm-2024/"},{"id":"paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","kind":"paper","name":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","route":"/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/"},{"id":"paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019","kind":"paper","name":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)","route":"/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/"},{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/"},{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/"},{"id":"paper-heymach-aegean-perioperative-durvalumab-nejm-2023","kind":"paper","name":"Perioperative durvalumab for resectable non-small-cell lung cancer","route":"/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/"},{"id":"paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023","kind":"paper","name":"Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/"},{"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-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-tumeh-pd1-adaptive-immune-resistance-nature-2014","kind":"paper","name":"Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge","route":"/key-papers/paper-tumeh-pd1-adaptive-immune-resistance-nature-2014/"}],"trial":[{"id":"checkmate-017","kind":"trial","name":"CheckMate 017","route":"/trials/checkmate-017/"},{"id":"checkmate-057","kind":"trial","name":"CheckMate 057","route":"/trials/checkmate-057/"},{"id":"checkmate-9la","kind":"trial","name":"CheckMate 9LA","route":"/trials/checkmate-9la/"},{"id":"nct07487805","kind":"trial","name":"ICONIC: ivermectin combined with immune checkpoint inhibition in cancer (University of Florida phase 2)","route":"/trials/nct07487805/"},{"id":"impower150","kind":"trial","name":"IMpower150","route":"/trials/impower150/"},{"id":"keynote-010","kind":"trial","name":"KEYNOTE-010","route":"/trials/keynote-010/"},{"id":"oak","kind":"trial","name":"OAK","route":"/trials/oak/"}],"journal":[{"id":"jitc","kind":"journal","name":"Journal for ImmunoTherapy of Cancer","route":"/journals/jitc/"},{"id":"targeted-oncology","kind":"journal","name":"Targeted oncology","route":"/journals/targeted-oncology/"}],"cancer":[{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}]}}