Focusing on CD8+ T-cell phenotypes: improving solid tumor therapy

Zhouchi Yao; Yayun Zeng; Cheng Liu; Huimin Jin; Hong Wang; Yue Zhang; Chengming Ding; Guodong Chen; Daichao Wu

doi:10.1186/s13046-024-03195-5

Focusing on CD8⁺ T-cell phenotypes: improving solid tumor therapy

J Exp Clin Cancer Res. 2024 Sep 28;43(1):266. doi: 10.1186/s13046-024-03195-5.

Authors

Zhouchi Yao¹, Yayun Zeng², Cheng Liu¹, Huimin Jin², Hong Wang³, Yue Zhang⁴, Chengming Ding⁵, Guodong Chen⁶, Daichao Wu^{7

8}

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Laboratory of Structural Immunology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
² Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
³ Department of Scientific Research, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121001, China.
⁴ Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. 2021000048@usc.edu.cn.
⁵ Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Laboratory of Structural Immunology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. 2018011096@usc.edu.cn.
⁶ Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Laboratory of Structural Immunology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. chenguodong@usc.edu.cn.
⁷ Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Laboratory of Structural Immunology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. wudaichao@usc.edu.cn.
⁸ Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. wudaichao@usc.edu.cn.

Abstract

Vigorous CD8⁺ T cells play a crucial role in recognizing tumor cells and combating solid tumors. How T cells efficiently recognize and target tumor antigens, and how they maintain the activity in the "rejection" of solid tumor microenvironment, are major concerns. Recent advances in understanding of the immunological trajectory and lifespan of CD8⁺ T cells have provided guidance for the design of more optimal anti-tumor immunotherapy regimens. Here, we review the newly discovered methods to enhance the function of CD8⁺ T cells against solid tumors, focusing on optimizing T cell receptor (TCR) expression, improving antigen recognition by engineered T cells, enhancing signal transduction of the TCR-CD3 complex, inducing the homing of polyclonal functional T cells to tumors, reversing T cell exhaustion under chronic antigen stimulation, and reprogramming the energy and metabolic pathways of T cells. We also discuss how to participate in the epigenetic changes of CD8⁺ T cells to regulate two key indicators of anti-tumor responses, namely effectiveness and persistence.

Keywords: CD8+ T cell; Engineered T cell receptor -T cells; Gene editing; Immune checkpoint; Immune reprogramming; Immunotherapy; Metabolic reprogramming; Solid tumor; T cell redirection.

Publication types

Review

MeSH terms

Animals
CD8-Positive T-Lymphocytes* / immunology
Humans
Immunotherapy / methods
Neoplasms* / immunology
Neoplasms* / therapy
Phenotype*
Tumor Microenvironment / immunology

Grants and funding

32270995;32100985/National Natural Science Foundation of China