Cancer immunotherapy by CTLA4 blockade (WP4582)

Homo sapiens

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 [ 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 [ CTLA4 Signaling Pathway] and [ Wikipedia].


Kristina Hanspers , Friederike Ehrhart , Egon Willighagen , and Eric Weitz


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Homo sapiens




Cell Type Ontology

professional antigen presenting cell T cell

Pathway Ontology

cancer pathway immune response pathway adaptive immune response pathway

Disease Ontology



Label Type Compact URI Comment
Ipilimumab Metabolite wikidata:Q2459042
Tremelimumab Metabolite wikidata:Q7838098
PPP2CA GeneProduct ensembl:ENSG00000113575
PTPN6 GeneProduct ensembl:ENSG00000111679
CD80 GeneProduct ensembl:ENSG00000121594
CD86 GeneProduct ensembl:ENSG00000114013
CTLA4 GeneProduct ensembl:ENSG00000163599
TRA GeneProduct ncbigene:6955
TRB GeneProduct ncbigene:6957
CD28 GeneProduct ensembl:ENSG00000178562
PTPN11 GeneProduct ensembl:ENSG00000179295
PIK3CA GeneProduct ensembl:ENSG00000121879 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18706
PIK3R1 GeneProduct ensembl:ENSG00000145675 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18708
PIK3R2 GeneProduct ensembl:ENSG00000105647 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18709
PIK3CB GeneProduct ensembl:ENSG00000051382 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:74769
PIK3CD GeneProduct ensembl:ENSG00000171608 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18707
PIK3R3 GeneProduct ensembl:ENSG00000117461 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:75669
MHC II Protein uniprot:D7RIH8


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