Harnessing the immune system by targeting immune checkpoints: Providing new hope for Oncotherapy

Abstract

With the goal of harnessing the host's immune system to provide long-lasting remission and cures for various cancers, the advent of immunotherapy revolutionized the cancer therapy field. Among the current immunotherapeutic strategies, immune checkpoint blockades have greatly improved the overall survival rates in certain patient populations. Of note, CTLA4 and PD-1/PD-L1 are two major non-redundant immune checkpoints implicated in promoting cancer immune evasion, and ultimately lead to relapse. Antibodies or inhibitors targeting these two c+heckpoints have achieved some encouraging clinical outcomes. Further, beyond the canonical immune checkpoints, more inhibitory checkpoints have been identified. Herein, we will summarize recent progress in immune checkpoint blockade therapies, with a specific focus on key pre-clinical and clinical results of new immune checkpoint therapies for cancer. Given the crucial roles of immune checkpoint blockade in oncotherapy, drugs targeting checkpoint molecules expressed by both cancer and immune cells are in clinical trials, which will be comprehensively summarized in this review. Taken together, investigating combinatorial therapies targeting immune checkpoints expressed by cancer cells and immune cells will greatly improve immunotherapies that enhance host elimination of tumors.

Keywords: T cell immunoglobulin and mucin-3 (Tim-3); cytotoxic T lymphocyte-associated antigen-4 (CTLA4); immune checkpoints; lymphocyte activation gene 3 (Lag-3); oncotherapy; programmed cell death 1 ligand 1 (PD-L1); programmed cell death protein 1 (PD-1).