Correlations between Circulating and Tumor-Infiltrating CD4 + T Cell Subsets with Immune Checkpoints in Colorectal Cancer

Al-Mterin, MA, Murshed, K ORCID: https://orcid.org/0000-0001-8045-363X and Elkord, E ORCID: https://orcid.org/0000-0002-3868-0318 2022, 'Correlations between Circulating and Tumor-Infiltrating CD4 + T Cell Subsets with Immune Checkpoints in Colorectal Cancer' , Vaccines, 10 (4) , e538.

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Abstract

T regulatory cells (Tregs) play different roles in the regulation of anti-tumor immunity in colorectal cancer (CRC), depending on the presence of different Treg subsets. We investigated correlations between different CD4+ Treg/T cell subsets in CRC patients with immune checkpoint-expressing CD4+ T cells. Positive correlations were observed between levels of different immune checkpoint-expressing CD4+ T cells, including PD-1, TIM-3, LAG-3, and CTLA-4 with FoxP3+ Tregs, Helios+ T cells, FoxP3+Helios+ Tregs, and FoxP3+Helios− Tregs in the tumor microenvironment (TME). However, negative correlations were observed between levels of these immune checkpoint-expressing CD4+ T with FoxP3−Helios− T cells in the TME. These correlations in the TME highlight the role of cancer cells in the upregulation of IC-expressing Tregs. Additionally, positive correlations were observed between levels of FoxP3+ Tregs, Helios+ T cells, FoxP3+Helios+ Tregs, and FoxP3+Helios− Tregs and levels of CD4+CTLA-4+ T cells and CD4+PD-1+ T cells in peripheral blood mononuclear cells (PBMCs) and normal tissue-infiltrating lymphocytes (NILs). These observations suggest that CTLA-4 and PD-1 expressions on CD4+ T cell subsets are not induced only by the TME. This is the first study to investigate the correlations of different FoxP3+/−Helios+/− T cell subsets with immune checkpoint-expressing CD4+ T cells in CRC patients. Our data demonstrated strong correlations between FoxP3+/Helios+/− Tregs but not FoxP3−Helios+/− non-Tregs and multiple immune checkpoints, especially in the TME, providing a rationale for targeting these cells with highly immunosuppressive characteristics. Understanding the correlations between different immune checkpoints and Treg/T cell subsets in cancer patients could improve our knowledge of the underlying mechanisms of Treg-mediated immunosuppression in cancer.

Item Type: Article
Journal or Publication Title: Vaccines
Publisher: MDPI
ISSN: 2076-393X
Related URLs:
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 16 May 2022 13:25
Last Modified: 16 May 2022 13:25
URI: http://usir.salford.ac.uk/id/eprint/63541

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