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Molecular Cancer
Published in: Molecular Cancer 1/2024

Open Access 01-12-2024 | Biomarkers | Review

CTLs heterogeneity and plasticity: implications for cancer immunotherapy

Authors: Shengkun Peng, Anqi Lin, Aimin Jiang, Cangang Zhang, Jian Zhang, Quan Cheng, Peng Luo, Yifeng Bai

Published in: Molecular Cancer | Issue 1/2024

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Abstract

Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.
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Metadata
Title
CTLs heterogeneity and plasticity: implications for cancer immunotherapy
Authors
Shengkun Peng
Anqi Lin
Aimin Jiang
Cangang Zhang
Jian Zhang
Quan Cheng
Peng Luo
Yifeng Bai
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Biomarkers
Published in
Molecular Cancer / Issue 1/2024
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-024-01972-6

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