Effect of Alpha1 Antitrypsin on PD-1/PD-L1 and EGFR in Colitis-Associated Colorectal Cancer BALB/c Mouse Model

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.

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).

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.

These findings suggest that AAT treatment has immunomodulatory properties and may represent a promising therapeutic strategy for colon cancer.