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Front. Immunol., 2023 Feb 20:14:1104771 | https://doi.org/10.3389/fimmu.2023.1104771 T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications

Xiaoxia Chi^1,†, Shahang Luo ^1,†, Peng Ye^2,†, Wei-Lun Hwang ^3,4, Jong-Ho Cha ^5,*, Xiuwen Yan ^1,*, Wen-Hao Yang ^6,*

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

^†These authors contributed equally

^*Corresponding authors: correspondence to Jong-Ho Cha, Xiuwen Yan or Wen-Hao Yang

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.

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