**1. Introduction**

Immune checkpoint inhibitor (ICI) is an established therapeutic strategy for various cancers. ICI comprises mainly of monoclonal antibodies that block immune regulatory checkpoint molecules, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Programmed cell death protein-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) [1]. To date, FDA has approved ICIs for various cancer types including anti-CTLA-4 (Ipilimumab, Tremelimumab), anti-PD-1 (Pembrolizumab, Nivolumab, Cemiplimab) and anti-PD-L1 (Atezolizumab, Avelumab, and Durvalumab) [2].

The main mechanism of action of immune checkpoint inhibitors is to target and augment host CD4+ and CD8+ T cell responses. Briefly, CTLA-4 is a T-cell surface receptor that binds costimulatory factors (CD80, CD86) on antigen-presenting cells. This activation transmits inhibitory signal to T cells thus, reducing Interleukin 2 (IL-2) production and T-cell proliferation. Moreover, PD-1 is a cell surface receptor expressed on B cells, T cells and NK cells. Its main function is to promote self-tolerance/ prevent autoimmunity via apoptosis of antigen-specific T-cells, suppression of T cell inflammatory activity and downregulation of the immune system. PD-1 has strong binding affinity to its ligands, PD-L1/PD-L2 and this binding delivers a strong inhibitory signal to suppress T cell receptor (TCR) mediated activation of IL-2 production and T cell proliferation for immune regulation [3].
