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

Abstract

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.

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