» Articles » PMID: 27192565

Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation

Overview
Journal Immunity
Publisher Cell Press
Date 2016 May 19
PMID 27192565
Citations 1082
Authors
Affiliations
Soon will be listed here.
Abstract

Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co-inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors, although they belong to the same class of receptors as PD-1 and CTLA-4, exhibit unique functions, especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic.

Citing Articles

Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.

Hu Q, Shi Y, Wang H, Bing L, Xu Z Exp Hematol Oncol. 2025; 14(1):37.

PMID: 40087690 DOI: 10.1186/s40164-025-00627-6.


Revolutionary Cancer Therapy for Personalization and Improved Efficacy: Strategies to Overcome Resistance to Immune Checkpoint Inhibitor Therapy.

Almawash S Cancers (Basel). 2025; 17(5).

PMID: 40075727 PMC: 11899125. DOI: 10.3390/cancers17050880.


Co-expression of B7-H3 and LAG3 represents cytotoxicity of CD4 T cells in humans.

Tamura Y, Ohki S, Nagai H, Yoshizato R, Nishi S, Jin Y Front Immunol. 2025; 16:1560383.

PMID: 40070836 PMC: 11893609. DOI: 10.3389/fimmu.2025.1560383.


Combination therapy with expanded natural killer cells and atezolizumab exerts potent antitumor immunity in small cell lung cancer.

Vo M, Nguyen V, Tran V, Oh H, Jung S, Bae W Cancer Immunol Immunother. 2025; 74(4):143.

PMID: 40056167 PMC: 11890499. DOI: 10.1007/s00262-025-03997-2.


Tumor-intrinsic PRMT5 upregulates FGL1 methylating TCF12 to inhibit CD8 T-cell-mediated antitumor immunity in liver cancer.

Sun J, Yuan H, Sun L, Zhao L, Wang Y, Hou C Acta Pharm Sin B. 2025; 15(1):188-204.

PMID: 40041915 PMC: 11873606. DOI: 10.1016/j.apsb.2024.10.016.


References
1.
G Casado J, Pawelec G, Morgado S, Sanchez-Correa B, Delgado E, Gayoso I . Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines. Cancer Immunol Immunother. 2009; 58(9):1517-26. PMC: 11030684. DOI: 10.1007/s00262-009-0682-y. View

2.
Monney L, Sabatos C, Gaglia J, Ryu A, Waldner H, Chernova T . Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002; 415(6871):536-41. DOI: 10.1038/415536a. View

3.
Huard B, Prigent P, Tournier M, Bruniquel D, Triebel F . CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins. Eur J Immunol. 1995; 25(9):2718-21. DOI: 10.1002/eji.1830250949. View

4.
Wu W, Shi Y, Li J, Chen F, Chen Z, Zheng M . Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection. Virol J. 2011; 8:113. PMC: 3061941. DOI: 10.1186/1743-422X-8-113. View

5.
Welch M, Teijaro J, Lewicki H, Colonna M, Oldstone M . CD8 T cell defect of TNF-α and IL-2 in DNAM-1 deficient mice delays clearance in vivo of a persistent virus infection. Virology. 2012; 429(2):163-70. PMC: 3571684. DOI: 10.1016/j.virol.2012.04.006. View