T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications

Xiaoxia Chi; Shahang Luo; Peng Ye; Wei-Lun Hwang; Jong-Ho Cha; Xiuwen Yan; Wen-Hao Yang

doi:10.3389/fimmu.2023.1104771

T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications

Front Immunol. 2023 Feb 20:14:1104771. doi: 10.3389/fimmu.2023.1104771. eCollection 2023.

Authors

Xiaoxia Chi¹, Shahang Luo¹, Peng Ye², Wei-Lun Hwang^{3

4}, Jong-Ho Cha⁵, Xiuwen Yan¹, Wen-Hao Yang⁶

Affiliations

¹ Affiliated Cancer Hospital & Institute and Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, Guangzhou Medical University, Guangzhou, Guangdong, China.
² Department of Infectious Diseases, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China.
³ Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴ Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁵ Department of Biomedical Science, College of Medicine, and Program in Biomedical Sciences and Engineering, Inha University, Incheon, Republic of Korea.
⁶ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.

Abstract

T cells play a crucial role in the regulation of immune response and are integral to the efficacy of cancer immunotherapy. Because immunotherapy has emerged as a promising treatment for cancer, increasing attention has been focused on the differentiation and function of T cells in immune response. In this review, we describe the research progress on T-cell exhaustion and stemness in the field of cancer immunotherapy and summarize advances in potential strategies to intervene and treat chronic infection and cancer by reversing T-cell exhaustion and maintaining and increasing T-cell stemness. Moreover, we discuss therapeutic strategies to overcome T-cell immunodeficiency in the tumor microenvironment and promote continuous breakthroughs in the anticancer activity of T cells.

Keywords: TSCM; cancer immunotherapy; chronic antigenic stimulation; exhaustion; stemness.

Publication types

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

MeSH terms

Cell Differentiation
Humans
Immunotherapy
Neoplasms* / therapy
T-Cell Exhaustion*
T-Lymphocytes
Tumor Microenvironment

Grants and funding

This work was supported by the Guangzhou key medical discipline construction project fund, the National Natural Science Foundation of China (82172789), the National Science and Technology Council, Taiwan (MOST 111-2320-B-039-061 and 111-2628-B-A49-017), an Innovative Research Grant from the National Health Research Institutes, Taiwan (NHRI- EX111-11010BI), a YingTsai Young Scholar Award (CMU108-YTY-04), the National Research Foundation of Korea grant funded by the Korea government Ministry of Science and ICT (MSIT; Grant Nos.2020R1C1C1005631 and 2021R1A4A1031856 to J-HC), a grant from the Yen Tjing Ling Medical Foundation (CI-111-15 to W-LH), a grant from the Ministry of Health and Welfare, Center of Excellence for Cancer Research (MOHW107-TDU-B-211-114019, 111W31208 to W-LH), and a grant from the Higher Education Sprout Project by the Ministry of Education (MOE) (110AC-D303 to W-LH).