Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine

SIMPLE SUMMARY: Colorectal cancer (CRC) begins when normal cells turn out of balance, and a tumor is formed in the lining of the colon or rectum. Cytotoxic T-lymphocyte protein 4 (CTLA-4) is a potent molecule that could inhibit T cell activation. Here, we analyzed this molecule in the tissue samples and cell lines of colorectal cancer to reveal the mechanism of this inhibitory molecule in CRC. Our result showed an increasing trend of CTLA-4 in tissues and cell lines. Finally, capecitabine as an approved drug in CRC could suppress this inhibitory molecule. It can be concluded that the inhibition of this inhibitory molecule can re-active the immune cells, especially T cells, in CRC patients, which boosts the immune cells against the tumor. ABSTRACT: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.