The Role of Immune Checkpoints in Cancer Progression

Immune checkpoint proteins are like two-faced swords that first act as gatekeepers of the immune system to protect the host from tissue damage. In contrast, these proteins can corroborate cancer progression by inhibiting tumor-specific immune responses. Here, we summarized the regulation and signaling cascade of immune checkpoints molecules (PD-1/PD-L1, CTLA-4, TIM3, TIGIT, LAG3, and BTLA), including their role in providing co-inhibitory signals for regulating T-cell response. The involvement of immune checkpoint molecules to drive cancer growth is elaborated with explanations about various anticancer strategies, such as (1) the overexpression of immune checkpoints in cancer cells, immune cells, or the surrounding environment leading to incapabilities of the tumor-specific immune response, (2) immune checkpoints interference to metabolic pathways then deplete nutrients needed by immune cells, (3) the interaction between immune checkpoints and regulatory T cells. Lastly, future challenges of immune checkpoint inhibitors are discussed briefly to get insight into their applicability in the clinical setting.