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

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