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

Al-Mterin, Mohammad A.; Murshed, Khaled; Elkord, Eyad

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.

Citation

Al-Mterin, M. A., Murshed, K., & Elkord, E. (2022). Correlations between Circulating and Tumor-Infiltrating CD4+ T Cell Subsets with Immune Checkpoints in Colorectal Cancer. Vaccines, 10(4), 538. https://doi.org/10.3390/vaccines10040538

• Journal Article Type: Article
• Acceptance Date: Mar 29, 2022
• Online Publication Date: Mar 30, 2022
• Publication Date: Mar 30, 2022
• Deposit Date: May 16, 2022
• Publicly Available Date: May 16, 2022
• Journal: Vaccines
• Publisher: MDPI
• Volume: 10
• Issue: 4
• Pages: 538
• DOI: https://doi.org/10.3390/vaccines10040538
• Keywords: correlation, FoxP3, Helios, Tregs, immune checkpoints, CRC
• Publisher URL: https://doi.org/10.3390/vaccines10040538
• Related Public URLs: https://www.mdpi.com/journal/vaccines/special_issues/cancer_vaccine