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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; Elkord, E

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


Authors

M Al-Mterin

K Murshed

A Alsalman

A Abu-Dayeh

E Elkord



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.

Citation

Al-Mterin, M., Murshed, K., Alsalman, A., Abu-Dayeh, A., & 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), 601. https://doi.org/10.1186/s12885-022-09710-1

Journal Article Type Article
Acceptance Date May 26, 2022
Publication Date Jun 2, 2022
Deposit Date Jul 29, 2022
Publicly Available Date Jul 29, 2022
Journal BMC Cancer
Publisher Springer Verlag
Volume 22
Issue 1
Pages 601
DOI https://doi.org/10.1186/s12885-022-09710-1
Publisher URL https://doi.org/10.1186/s12885-022-09710-1

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