Associations of different immune checkpoints-expressing CD4 + Treg/ T cell subsets with disease-free survival in colorectal cancer patients

Al-Mterin, M, Murshed, K, Alsalman, A, Abu-Dayeh, A and Elkord, E 2022, 'Associations of different immune checkpoints-expressing CD4 + Treg/ T cell subsets with disease-free survival in colorectal cancer patients' , BMC Cancer, 22 (1) , p. 601.

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Abstract

There are different subsets of T regulatory cells (Tregs), orchestrating critical roles in the regulation of anti-tumor immunity in colorectal cancer (CRC). In this study, we report that a high frequency of circulating CD4+FoxP3+ Tregs was associated with poorer disease-free survival (DFS), while their higher frequencies in tumor-infiltrating CD4+ Tregs was associated with better DFS. We further investigated such associations with four Tregs/T cells expressing or lacking FoxP3 and Helios (FoxP3±Helios±). For the first time, we report that a high frequency of circulating CD4+FoxP3+Helios+ Tregs was associated with poorer DFS, while a high frequency of tumor-infiltrating CD4+FoxP3−Helios− T cells was associated with poorer DFS. In the four FoxP3±Helios± T cell subsets expressing any of the immune checkpoints (ICs) investigated, we found that a high frequency of CD4+FoxP3+Helios−PD-1+ Tregs in circulation was associated with worse DFS. We also found that high frequencies of FoxP3+Helios+CTLA-4+ Tregs, FoxP3+Helios−CTLA-4+ Tregs, and FoxP3−Helios+CTLA-4+ CD4+ T cells in circulation were associated with worse DFS. In contrast, high frequencies of CD4+TIM-3+ T cells, FoxP3+Helios+TIM-3+ Tregs, and FoxP3−Helios+TIM-3+ CD4+ T cells in circulation were associated with longer DFS. Our data show that certain CD4+ Treg/T cell subsets could serve as independent predictive biomarkers in CRC patients. Identification of the exact subpopulations contributing to clinical outcomes is critical for prognoses and therapeutic targeting.

Item Type: Article
Schools: Schools > School of Computing, Science and Engineering
Schools > School of Environment and Life Sciences
Journal or Publication Title: BMC Cancer
Publisher: BioMed Central
ISSN: 1471-2407
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 29 Jul 2022 13:30
Last Modified: 29 Jul 2022 13:30
URI: http://usir.salford.ac.uk/id/eprint/64080

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