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]. f09 c47 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18706 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18708 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18709 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:74769 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18707 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:75669 af6 daf af4 b57 f7e b19 f7e b19 19426232 PubMed Molecular mechanisms of T-cell receptor and costimulatory molecule ligation/blockade in autoimmune disease therapy. Immunol Rev 2009 Podojil JR Miller SD 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 professional antigen presenting cell CL:0000145 Cell Type T cell CL:0000084 Cell Type cancer pathway PW:0000605 Pathway Ontology immune response pathway PW:0000023 Pathway Ontology 21904389 PubMed New insights into the T cell synapse from single molecule techniques. Nat Rev Immunol 2011 Dustin ML Depoil D adaptive immune response pathway PW:0000235 Pathway Ontology cancer DOID:162 Disease 1191089 PubMed The drug surveillance program at the Arizona Medical Center. Ariz Med 1975 Trinca C Bressler R Walson P 8596936 PubMed Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996 Leach DR Krummel MF Allison JP 16551244 PubMed A molecular perspective of CTLA-4 function. Annu Rev Immunol 2006 Teft WA Kirchhof MG Madrenas J 22116087 PubMed The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol 2011 Walker LS Sansom DM 29339377 PubMed Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade. Cancer Immunol Res 2018 Ariyan CE Brady MS Siegelbaum RH Hu J Bello DM Rand J Fisher C Lefkowitz RA Panageas KS Pulitzer M Vignali M Emerson R Tipton C Robins H Merghoub T Yuan J Jungbluth A Blando J Sharma P Rudensky AY Wolchok JD Allison JP