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

Seongju Jeong; Su-Hyung Park

doi:10.4110/in.2020.20.e3

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

Review Article

Immune Netw 2020;20(1):e3.

Published online: 4 February 2020

DOI: https://doi.org/10.4110/in.2020.20.e3

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

Seongju Jeong¹, Su-Hyung Park^1,^2,^*

¹Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon 34141, Korea

²Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea

^*Correspondence to Su-Hyung Park Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea. E-mail: park3@kaist.ac.kr

Conflicts of Interest The authors declare no potential conflicts of interest.

Received 5 January 2020 Revised 27 January 2020 Accepted 27 January 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

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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.

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