Abstract
OBJECTIVE: This study aimed to investigate whether Human alpha-1 antitrypsin affects Programmed cell death protein 1 (PD-1) and its ligand (PD-L1) as well as epidermal growth factor receptor (EGFR) expression using a colon cancer tissues in chemically induced colorectal cancer (CRC) model. Previous study indicated a protective role of AAT administration on the development of cancer in CRC mouse model. METHODOLOGY: The expression of PD1/PDL1 and EGFR were analyzed in colon cancer tissue collected from (AOM/DSS) CRC mice using both real time gene expression (qPCR) and immunohistochemistry(IHC). RESULTS: Study results showed that AAT treatment reduced PD-L1 protein expression by 63.5% (mean H score: 7.8±1.3 to 2.85±0.85, p=0.0004) and EGFR protein expression by 48.9% (mean H score: 1.78±0.76 to 0.91±0.60, p=0.04) in the tissue of AOM/DSS-treated mice. In addition, AAT treatment controlled PD1 gene expression and repressed EGFR gene expression by 1.4-fold compared to DSS samples. Immunohistochemical analysis revealed various degrees of PD1 protein expression, and CD4 and CD8 positive lymphocytes were found in the tumor microenvironment. CONCLUSION: These findings suggest that AAT treatment has immunomodulatory properties and may represent a promising therapeutic strategy for colon cancer.