The nexus of dynamic T cell states and immune checkpoint blockade therapy in the periphery and tumor microenvironment

Hong Luo; Wenxiang Wang; Jia Mai; Rutie Yin; Xuyu Cai; Qintong Li

doi:10.3389/fimmu.2023.1267918

The nexus of dynamic T cell states and immune checkpoint blockade therapy in the periphery and tumor microenvironment

Front Immunol. 2023 Oct 10:14:1267918. doi: 10.3389/fimmu.2023.1267918. eCollection 2023.

Authors

Hong Luo¹, Wenxiang Wang², Jia Mai¹, Rutie Yin¹, Xuyu Cai³, Qintong Li¹

Affiliations

¹ Department of Obstetrics & Gynecology, Laboratory Medicine and Pediatrics, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan, China.
³ Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract

Immune checkpoint blockade (ICB) therapies, that is, using monoclonal antibodies to reinvigorate tumor-reactive, antigen-specific T cells from the inhibitory effects of CTLA-4, PD-1 and PD-L1 immune checkpoints, have revolutionized the therapeutic landscape of modern oncology. However, only a subset of patients can benefit from the ICB therapy. Biomarkers associated with ICB response, resistance and prognosis have been subjected to intensive research in the past decade. Early studies focused on the analysis of tumor specimens and their residing microenvironment. However, biopsies can be challenging to obtain in clinical practice, and do not reflect the dynamic changes of immunological parameters during the ICB therapy. Recent studies have investigated profiles of antigen-specific T cells derived from the peripheral compartment using multi-omics approaches. By tracking the clonotype and diversity of tumor-reactive T cell receptor repertoire, these studies collectively establish that de novo priming of antigen-specific T cells in peripheral blood occurs throughout the course of ICB, whereas preexisting T cells prior to ICB are exhausted to various degrees. Here, we review what is known about ICB-induced T cell phenotypic and functional changes in cancer patients both within the tumor microenvironment and in the peripheral compartment. A better understanding of parameters influencing the response to ICBs will provide rationales for developing novel diagnostics and combinatorial therapeutic strategies to maximize the clinical efficacies of ICB therapies.

Keywords: PD-1; PD-L1; T cell; TCR repertoire; immune checkpoint blockade; immunotherapy; peripheral blood; single-cell analysis.

Publication types

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

MeSH terms

Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Neoplasms* / drug therapy
Radioimmunotherapy
T-Lymphocytes*
Tumor Microenvironment

Substances

Immune Checkpoint Inhibitors

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. The National Natural Science Foundation of China (Both to QL) (No.31971141, No.32271348), the National Natural Science Foundation of China (to XC) (No.81972911), and the Science and Technology Department of Sichuan Province (to QL)(2021YJ0012).