T cell exhaustion in human cancers

Kuan Kang; Xin Lin; Pan Chen; Huai Liu; Feng Liu; Wei Xiong; Guiyuan Li; Mei Yi; Xiayu Li; Hui Wang; Bo Xiang

doi:10.1016/j.bbcan.2024.189162

T cell exhaustion in human cancers

Biochim Biophys Acta Rev Cancer. 2024 Sep;1879(5):189162. doi: 10.1016/j.bbcan.2024.189162. Epub 2024 Jul 30.

Authors

Kuan Kang¹, Xin Lin¹, Pan Chen², Huai Liu³, Feng Liu³, Wei Xiong¹, Guiyuan Li¹, Mei Yi⁴, Xiayu Li⁵, Hui Wang⁶, Bo Xiang⁷

Affiliations

¹ Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410078, Hunan, China.
² Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China.
³ Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
⁴ Department of Dermatology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
⁵ Hunan Key Laboratory of Nonresolving Infammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China. Electronic address: lixiayu@csu.edu.cn.
⁶ Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China. Electronic address: wanghui@hnszlyy.com.
⁷ Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410078, Hunan, China; FuRong Laboratory, Changsha 410078, Hunan, China. Electronic address: xiangbolin@csu.edu.cn.

PMID: 39089484
DOI: 10.1016/j.bbcan.2024.189162

Abstract

T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread. In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression. We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances. The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion. Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors.

Keywords: Immune checkpoint; Immune evasion; Immune inhibitory receptors; Immunotherapy; T cell exhaustion.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Epigenesis, Genetic
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Immunotherapy / methods
Immunotherapy, Adoptive / methods
Neoplasms* / immunology
Neoplasms* / pathology
Neoplasms* / therapy
T-Cell Exhaustion
T-Lymphocytes* / immunology
Tumor Escape
Tumor Microenvironment* / immunology

Substances

Immune Checkpoint Inhibitors