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 [2018 Nobel prize in Physiology or Medicine](https://www.nobelprize.org/prizes/medicine/2018/summary/) 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 [Pardoll](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856023/) and figure 1 in the review by [Sharpe and Pauken](https://www.ncbi.nlm.nih.gov/pubmed/28990585).