An Overview of Immune Checkpoints and Immunotherapy in Cancer

Abstract

Immune checkpoints are molecules in the immune system that either turn-on a signal (co-stimulatory molecules) or turn-off a signal for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses. Many cancers protect themselves from the immune system by inhibiting the T cell signal Inhibitory receptors such as anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), expressed on tumor-specific T cells, lead to compromised activation and suppressed effector functions such as proliferation, cytokine secretion, and tumour cell lysis. Modulating these receptors using monoclonal antibodies, an approach termed “immune checkpoint blockade,” has gained momentum as a new approach in cancer immunotherapy. This treatment concept was first introduced in patients with advanced melanoma: In this patient population, the anti-CTLA-4 antibody Ipilimumab was the first drug ever to show improved overall survival in phase III trials. Antibodies directed against PD-1 and its ligand, PD-L1, have shown much promise in the treatment of melanoma, renal cell cancer, non-small cell lung cancer, and other tumours, as evident by encouraging rates and durability of tumour responses. Because of the successes with immune checkpoint inhibitors in cancer immunotherapy, many new agents and strategies, including combination approaches, are being developed at a fast pace.