Immune checkpoints are hardwired into the immune system and are crucial for maintaining self-tolerance. Tumors can use these checkpoints to protect themselves from immune system attacks. One such immune checkpoint is PD-1 (programmed cell death 1 protein), which binds to its ligand PD-L1 and inhibits immune cell activity, including T cell activity. By upregulating PD-L1, cancer cells can inhibit T cells that might otherwise attack. One strategy for cancer immunotherapy is to block this kind of negative feedback, thereby increasing anti-cancer T-cell activity. For the PD-1 checkpoint, cancer immunotherapeutics block either the PD-1 receptor, or the PD-L1 ligand. The [https://www.nobelprize.org/prizes/medicine/2018/summary/ 2018 Nobel prize in Physiology or Medicine] was awarded to jointly to James Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org. Based on and figure 4B in the review by [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856023/ Pardoll] and figure 1 in the review by [https://www.ncbi.nlm.nih.gov/pubmed/28990585 Sharpe and Pauken]. c58 f89 bda a66 https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-pd-1-fusion-protein-amp-224 parentid=Q15116; parentsymbol=PDCD1; site=CVPEQTEyATIVFPS; position=tyr248; sitegrpid=50293001; ptm=p; direction=u parentid=P43403; parentsymbol=ZAP70; site=tsVyEsPysDPEELk; position=tyr319; sitegrpid=447587; ptm=p; direction=u parentid=P43403; parentsymbol=ZAP70; site=VLLVNRHyAkISDFG; position=tyr474; sitegrpid=455368; ptm=p; direction=u parentid=Q15116; parentsymbol=PDCD1; site=VPVFSVDyGELDFQW; position=tyr223; sitegrpid=450293000; ptm=p; direction=u abc e61 ca1 28990585 PubMed The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 2018 Sharpe AH Pauken KE cancer pathway PW:0000605 Pathway Ontology 29347993 PubMed Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer 2018 Kaufman HL Russell JS Hamid O Bhatia S Terheyden P D'Angelo SP Shih KC Lebbé C Milella M Brownell I Lewis KD Lorch JH von Heydebreck A Hennessy M Nghiem P cancer DOID:162 Disease 30345906 PubMed Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018 Schmid P Adams S Rugo HS Schneeweiss A Barrios CH Iwata H Diéras V Hegg R Im SA Shaw Wright G Henschel V Molinero L Chui SY Funke R Husain A Winer EP Loi S Emens LA 30511409 PubMed Immune checkpoint blockade opens a new way to cancer immunotherapy. J Cell Physiol 2019 Sadreddini S Baradaran B Aghebati-Maleki A Shanehbandi D Fotouhi A Aghebati-Maleki L 22437870 PubMed The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012 Pardoll DM 28643244 PubMed Durvalumab: First Global Approval. Drugs 2017 Syed YY adaptive immune response pathway PW:0000235 Pathway Ontology 25514926 PubMed PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res 2015 Hornbeck PV Zhang B Murray B Kornhauser JM Latham V Skrzypek E T cell CL:0000084 Cell Type