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Correlations between Circulating and Tumor-Infiltrating CD4 + T Cell Subsets with Immune Checkpoints in Colorectal Cancer.
- Source :
- Vaccines; Apr2022, Vol. 10 Issue 4, pN.PAG-N.PAG, 12p
- Publication Year :
- 2022
-
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<superscript>+</superscript> Treg/T cell subsets in CRC patients with immune checkpoint-expressing CD4<superscript>+</superscript> T cells. Positive correlations were observed between levels of different immune checkpoint-expressing CD4<superscript>+</superscript> T cells, including PD-1, TIM-3, LAG-3, and CTLA-4 with FoxP3<superscript>+</superscript> Tregs, Helios<superscript>+</superscript> T cells, FoxP3<superscript>+</superscript>Helios<superscript>+</superscript> Tregs, and FoxP3<superscript>+</superscript>Helios<superscript>−</superscript> Tregs in the tumor microenvironment (TME). However, negative correlations were observed between levels of these immune checkpoint-expressing CD4<superscript>+</superscript> T with FoxP3<superscript>−</superscript>Helios<superscript>−</superscript> 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<superscript>+</superscript> Tregs, Helios<superscript>+</superscript> T cells, FoxP3<superscript>+</superscript>Helios<superscript>+</superscript> Tregs, and FoxP3<superscript>+</superscript>Helios<superscript>−</superscript> Tregs and levels of CD4<superscript>+</superscript>CTLA-4<superscript>+</superscript> T cells and CD4<superscript>+</superscript>PD-1<superscript>+</superscript> 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<superscript>+</superscript> T cell subsets are not induced only by the TME. This is the first study to investigate the correlations of different FoxP3<superscript>+/−</superscript>Helios<superscript>+/−</superscript> T cell subsets with immune checkpoint-expressing CD4<superscript>+</superscript> T cells in CRC patients. Our data demonstrated strong correlations between FoxP3<superscript>+/</superscript>Helios<superscript>+/−</superscript> Tregs but not FoxP3<superscript>−</superscript>Helios<superscript>+/−</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2076393X
- Volume :
- 10
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Vaccines
- Publication Type :
- Academic Journal
- Accession number :
- 156624900
- Full Text :
- https://doi.org/10.3390/vaccines10040538