4.3 Article

The Expression of Immune Checkpoint Receptors and Ligands in the Colorectal Cancer Tumor Microenvironment

Journal

ANTICANCER RESEARCH
Volume 41, Issue 10, Pages 4895-4905

Publisher

INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.15303

Keywords

Colorectal cancer; PD-1; TIM-3; TIGIT; PD-L1; CEACAM-1; CD155

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The study indicates that the PD-1, TIM-3, and TIGIT axes may reduce T cell function in the colorectal cancer tumor microenvironment.
Background/Aim: The limited efficacy of immune checkpoint inhibitors in colorectal cancer (CRC) is likely due to immunosuppressive mechanisms including T cell exhaustion caused by inhibitory immune checkpoints in the tumor microenvironment. Materials and Methods: We investigated the expression status of the inhibitory immune checkpoint receptors on tumor-infiltrating T cells and their ligands on tumor cells by flow cytometry and immunohistochemistry, using surgically-resected specimens of CRC. Results: Flow cytometry analysis indicated that TIM-3, TIGIT, and PD-1 were expressed on tumor-infiltrating CD4+ (8.3%, 56.0%, 26.1%) and CD8+ T cells (8.2%, 51.6%, 23.5%), and CRC cells abundantly expressed PD- L1, CEACAM-1, and CD155 (2.2%, 77.0%, 46.8%). Immunohistochemical analysis revealed that the tumor proportional score of PD-L1, CEACAM-1, and CD155 was 42.4%, 54.2%, and 52.1%, respectively. Conclusion: PD-1, TIM-3, and TIGIT axes may reduce T cell function in the CRC tumor microenvironment.

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