West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 26 9 2025 09 01 Effect of Alpha1 Antitrypsin on PD-1/PD-L1 and EGFR in Colitis-Associated Colorectal Cancer BALB/c Mouse Model 3229 3237 91826 10.31557/APJCP.2025.26.9.3229 EN Mariam M. Al-Omari Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan. Ayman Okour Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan. Khaled M. Al-Qaoud Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan. 0000-0002-4453-8190 Tareq Al-Omari Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan. Roaa H Marashdeh Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan. Nesreen M. Bataineh Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan. Journal Article 2024 11 01 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. https://journal.waocp.org/article_91826_81f3b7f138374fcc3cf6751d26ab0f59.pdf