Skip to main content

Research Repository

Advanced Search

Circulating and tumor-infiltrating immune checkpoint-xepressing CD8+ Treg/T Cell subsets and their associations with disease-free survival in colorectal cancer patients

Alsalman, A; Al-Mterin, MA; Murshed, K; Alloush, F; Al-Shouli, ST; Toor, SM; Elkord, E

Circulating and tumor-infiltrating immune checkpoint-xepressing CD8+ Treg/T Cell subsets and their associations with disease-free survival in colorectal cancer patients Thumbnail


Authors

A Alsalman

MA Al-Mterin

K Murshed

F Alloush

ST Al-Shouli

SM Toor

E Elkord



Abstract

T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity, including orchestration of immune responses and anti-tumor cytotoxic attack. However, different T cell subsets may have opposing roles in tumor progression, especially in inflammation-related cancers such as colorectal cancer (CRC). In this study, we phenotypically characterized CD3+CD4- (CD8+) T cells in colorectal tumor tissues (TT), normal colon tissues (NT) and in circulation of CRC patients. We investigated the expression levels of key immune checkpoints (ICs) and Treg-related markers in CD8+ T cells. Importantly, we investigated associations between different tumor-infiltrating CD8+ T cell subpopulations and disease-free survival (DFS) in CRC patients. We found that FoxP3 expression and ICs including PD-1, CTLA-4, TIM-3, and LAG-3 were significantly increased in tumor-infiltrating CD8+ T cells compared with NT and peripheral blood. In the TME, we found that TIM-3 expression was significantly increased in patients with early stages and absent lymphovascular invasion (LVI) compared to patients with advanced stages and LVI. Importantly, we report that high levels of certain circulating CD8+ T cell subsets (TIM-3-expressing, FoxP3-Helios-TIM-3+ and FoxP3-Helios+TIM-3+ cells) in CRC patients were associated with better DFS. Moreover, in the TME, we report that elevated levels of CD25+ and TIM-3+ T cells, and FoxP3+Helios-TIM-3+ Tregs were associated with better DFS.

Citation

Alsalman, A., Al-Mterin, M., Murshed, K., Alloush, F., Al-Shouli, S., Toor, S., & Elkord, E. (2022). Circulating and tumor-infiltrating immune checkpoint-xepressing CD8+ Treg/T Cell subsets and their associations with disease-free survival in colorectal cancer patients. Cancers, 14(13), 3194. https://doi.org/10.3390/cancers14133194

Journal Article Type Article
Acceptance Date Jun 1, 2022
Online Publication Date Jun 29, 2022
Publication Date Jun 29, 2022
Deposit Date Sep 6, 2022
Publicly Available Date Sep 6, 2022
Journal Cancers
Publisher MDPI
Volume 14
Issue 13
Pages 3194
DOI https://doi.org/10.3390/cancers14133194
Publisher URL https://doi.org/10.3390/cancers14133194
Related Public URLs https://europepmc.org/articles/PMC9265020

Files




Downloadable Citations