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overall patient survival. Current FDA approved PD-1/PD-L1 inhibitors include Nivolumab and Pembrolizumab which are PD-1 inhibitors and Atezolizumab which is a PD-L1 inhibitor. These are currently the frontline treatments for metastatic melanoma, non-small cell lung cancer, renal cell carcinoma and urothelial cancer.

Immune mediated adverse reactions describe the side effects of immunotherapy. PD-1/PD-L1 inhibitors can have adverse reactions that lead to immune system dysregulation which can cause autoimmune disease-like symptoms. Classic chemotherapy toxicities (fatigue, anorexia, nausea, diarrhea), are also seen in patients treated with PD-1/PD-L1 inhibitors. These adverse effects are likely due to off-target interactions.

PD-1/PD-L1 inhibitors are closely related to CTLA-4 inhibitors as both PD-1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) are expressed on activated T cells. The difference between the two inhibitors is the phase of the immune response in which they are active. While PD-1 inhibitors target T-cell activation in the tumor environment, anti-CTLA-4 antibodies centrally affect T-cell priming.

CTLA-4 is an immune checkpoint that stops and inactivates autoreactive T-cells that are unable to differentiate self from non-self, at the initial stage of activation in the lymph nodes. Activation of the CTLA-4 receptor downregulates any immunogenic response by binding to its ligands CD80 and CD86. The CTLA-4 receptor is expressed by both CD4+ (helper) and CD8+ (cytotoxic) T-cells while its ligands are pres