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.
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