Recent advances in the clinical development of immune checkpoint blockade therapy

Abstract

Background: The discovery of immune checkpoint proteins and the mechanisms by which cancer cells utilize them to evade the immune system has transformed our approach to cancer immunotherapy. Checkpoint blockade antibodies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligands such as programmed cell death ligand 1 (PD-L1) have already revolutionized the treatment of multiple types of cancer and have significantly improved treatment and survival outcomes of patients affected by these malignancies.

Conclusions: Herein, we summarize current knowledge about the role of, and the mechanisms underlying PD-1/PD-L1 signaling pathways in antitumor immune responses, with particular emphasis on clinical studies evaluating the efficacy of anti-PD-1/PD-L1 blockade in various tumor types. Preliminary clinical investigations with immune-checkpoint blockers highlight broad opportunities with a high potential to enhance antitumor immunity and, as such, to generate significant clinical responses. These preliminary successes open up new avenues towards efficient therapeutics offered to patients.

Keywords: Cancer immunotherapy; Checkpoint inhibitors; Combination immune therapy; Immune checkpoint blockade antibodies; Immune resistance; PD-1/PDL-1 mechanism.