Cancer immunotherapy by PD-1 blockade (WP4585)
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].
AuthorsKristina Hanspers , Friederike Ehrhart , and Egon Willighagen
Discuss this pathway
- DNA methylation of ARHGAP30 is negatively associated with ARHGAP30 expression in lung adenocarcinoma, which reduces tumor immunity and is detrimental to patient survival (2021).
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
OrganismsHomo sapiens CPTAC
Pathway Ontologycancer pathway adaptive immune response pathway
Cell Type OntologyT cell
- The blockade of immune checkpoints in cancer immunotherapy. Pardoll DM. Nat Rev Cancer. 2012 Mar 22;12(4):252–64. PubMed Europe PMC Scholia
- PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
- Durvalumab: First Global Approval. Syed YY. Drugs. 2017 Aug;77(12):1369–76. PubMed Europe PMC Scholia
- The diverse functions of the PD1 inhibitory pathway. Sharpe AH, Pauken KE. Nat Rev Immunol. 2018 Mar;18(3):153–67. PubMed Europe PMC Scholia
- 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. Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D’Angelo SP, et al. J Immunother Cancer. 2018 Jan 19;6(1):7. PubMed Europe PMC Scholia
- Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. N Engl J Med. 2018 Nov 29;379(22):2108–21. PubMed Europe PMC Scholia
- Immune checkpoint blockade opens a new way to cancer immunotherapy. Sadreddini S, Baradaran B, Aghebati-Maleki A, Sadreddini S, Shanehbandi D, Fotouhi A, et al. J Cell Physiol. 2019 Jun;234(6):8541–9. PubMed Europe PMC Scholia