Cancer immunotherapy by PD-1 blockade (WP4585)

Homo sapiens

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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].

Authors

Kristina Hanspers , Friederike Ehrhart , and Egon Willighagen

Activity

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Organisms

Homo sapiens

Communities

CPTAC

Annotations

Pathway Ontology

cancer pathway adaptive immune response pathway

Disease Ontology

cancer

Cell Type Ontology

T cell

Participants
Query Drugst.One

Label Type Compact URI Comment
Pembrolizumab Metabolite wikidata:Q13896859
Nivolumab Metabolite wikidata:Q7041828
Pidilizumab Metabolite wikidata:Q7191298
Durvalumab Metabolite wikidata:Q19904005
Avelumab Metabolite wikidata:Q21083261
Atezolizumab Metabolite wikidata:Q20707748
Tislelizumab Metabolite kegg.drug:D11487
CD8A GeneProduct ensembl:ENSG00000153563
CD274 GeneProduct ensembl:ENSG00000120217
IFNG GeneProduct ensembl:ENSG00000111537
PDCD1LG2 GeneProduct ensembl:ENSG00000197646
STAT3 GeneProduct ensembl:ENSG00000168610
TRA GeneProduct ncbigene:6955
JUN GeneProduct ensembl:ENSG00000177606
BATF GeneProduct ensembl:ENSG00000156127
CD3D GeneProduct ensembl:ENSG00000167286
ZAP70 GeneProduct ensembl:ENSG00000115085
LCK GeneProduct ensembl:ENSG00000182866
NFATC1 GeneProduct ensembl:ENSG00000131196
PDCD1 GeneProduct ensembl:ENSG00000188389
PTPN11 GeneProduct ensembl:ENSG00000179295
TRB GeneProduct ncbigene:6957
BATF GeneProduct ensembl:ENSG00000156127
CD3E GeneProduct ensembl:ENSG00000198851
CD3G GeneProduct ensembl:ENSG00000160654
NFKB1 GeneProduct ensembl:ENSG00000109320
CD8B GeneProduct ensembl:ENSG00000172116
NFATC2 GeneProduct ensembl:ENSG00000101096
NFATC3 GeneProduct ensembl:ENSG00000072736
NFATC4 GeneProduct ensembl:ENSG00000100968
NFAT5 GeneProduct ensembl:ENSG00000102908
MHC I Protein ensembl:ENSG00000206503
MHC II Protein ensembl:ENSG00000196126

References

  1. The blockade of immune checkpoints in cancer immunotherapy. Pardoll DM. Nat Rev Cancer. 2012 Mar 22;12(4):252–64. PubMed Europe PMC Scholia
  2. 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
  3. Durvalumab: First Global Approval. Syed YY. Drugs. 2017 Aug;77(12):1369–76. PubMed Europe PMC Scholia
  4. 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
  5. 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
  6. 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
  7. 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