The following is a summary of “CTLs heterogeneity and plasticity: implications for cancer immunotherapy,” published in the March 2024 issue of Oncology by Peng et al
Cytotoxic T lymphocytes (CTLs) are pivotal players in antitumor immunity, encompassing various subsets such as CD4+, NK, and γδ T cells, alongside conventional CD8+ CTLs. Despite their importance, identifying definitive CTLs biomarkers remains challenging, as the expression of cytotoxicity molecules does not always correlate with actual cytotoxic capacity. CTLs differentiation involves intricate transcriptional regulation by factors like T-bet and Blimp-1, although the role of epigenetic regulation in CTLs remains less understood.
While CTLs exert tumor-killing effects through mechanisms involving cytotoxic granules and death receptor pathways, they can paradoxically promote tumorigenesis in certain contexts. Given the variability in CTLs cytotoxicity among different tumors, enhancing this function is a crucial objective. This review comprehensively summarizes the current understanding of CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for augmenting cytotoxicity. Critical unresolved questions include refining the definition of CTLs, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe interactions, and enabling multi-omics profiling. A deeper comprehension of CTLs biology promises to optimize their therapeutic applications in immunotherapy.
This synthesis underscores the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity while emphasizing the gaps in their knowledge regarding subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these knowledge gaps will refine their understanding of CTLs immunology, enhancing their ability to harness their cytotoxic functions against cancer.
Source: molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01972-6