Cancer immunotherapy by CTLA4 blockade (WP4582)

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. CTLA-4 is expressed on T cells and is a negative regulator of T cell activation. CTLA4 counteracts the activity of the T cell co-stimulatory receptor, CD28, which amplifies TCR signaling once antigen is bound. CTLA-4 and CD28 share the same ligands, CD80 and CD86, although CTLA-4 has a higher affinity. This is represented in the pathway with a blue inhibitory interaction. One strategy for cancer immunotherapy is to block CTLA-4, thereby removing the negative regulation on T-cell activation. The first checkpoint antibody approved by the FDA was ipilimumab, approved in 2011 for treatment of melanoma. 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. Partially based on Thermo Fisher [https://www.thermofisher.com/us/en/home/life-science/antibodies/antibodies-learning-center/antibodies-resource-library/cell-signaling-pathways/ctla4-signaling-pathway.html CTLA4 Signaling Pathway] and [https://en.wikipedia.org/wiki/Immune_checkpoint Wikipedia].
last edited

Authors

Khanspers and Fehrhart

Cited In

Organism

Homo sapiens

Communities

CPTAC

Annotations

Disease Ontology: cancer

Cell Type Ontology: T cell professional antigen presenting cell

Pathway Ontology: adaptive immune response pathway immune response pathway cancer pathway

Participants

Label Type Compact Identifier
TCR Signaling Pathway wikipathways:WP69
PPP2CA GeneProduct ensembl:ENSG00000113575
Akt Signaling Pathway wikipathways:WP4172
Ipilimumab Metabolite wikidata:Q2459042
Tremelimumab Metabolite wikidata:Q7838098
PTPN6 GeneProduct ensembl:ENSG00000111679
CD80 GeneProduct ensembl:ENSG00000121594
CD86 GeneProduct ensembl:ENSG00000114013
Tumor-associatedantigen GeneProduct None
MHC II Protein uniprot:D7RIH8
CTLA4 GeneProduct ensembl:ENSG00000163599
TRA GeneProduct ncbigene:6955
TRB GeneProduct ncbigene:6957
CD28 GeneProduct ensembl:ENSG00000178562
PTPN11 GeneProduct ensembl:ENSG00000179295
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3CD GeneProduct ensembl:ENSG00000171608
PIK3R3 GeneProduct ensembl:ENSG00000117461

References

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