Co-Stimulatory Receptors in Cancers and Their Implications for Cancer Immunotherapy

Abstract

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

Keywords: Cancer, Immunotherapy; Costimulatory T-cell receptors; T-Lymphocytes.

Figure 1. Schematic overview of co-stimulatory/inhibitory receptors expressed by T cells interacting with their counterpart on APCs or tumor cells. Inhibitory and stimulatory receptors expressed on T cells in the tumor microenvironment may be targeted for therapeutic intervention by development of agonist targeting co-stimulatory receptors and/or blocking Abs targeting immune inhibitory receptors.

CD40L, CD40 ligand; LIGHT, lymphocyte activation gene 3 protein; HVEM, herpes virus-entry mediator; BTLA, B-lymphocyte and T-lymphocyte attenuator.