Abstract 2990: Role of CCR6-CCL20 chemokine axis in colon cancer

Abstract

Abstract Colon cancer remains the third leading cause of cancer-related deaths because chemotherapeutics currently offered to treat early, and advanced colon cancer fail to achieve optimal clinical response. Therefore, development of more efficacious treatment option is crucial to improve clinical outcomes. We have used TCGA and CPTAC analysis from UALCAN data base for the expression of CCR6 and CCL20 in colon cancer tissue compared to adjacent normal. RT-qPCR and proteomics approach were used for analysis of CCR6 and CCL20 expression in colon cancer cell lines. Our data shows higher expression of CCR6 and its ligand CCL20 in colon cancer tissue and cell lines. We further investigated involvement of CCR6/CCL20 on therapeutic response of 5-Fluorouracil and Oxaliplatin commonly used to treat colon cancer. Our data suggest that colon cancer cell lines respond poorly to 5-Fluorouracil and Oxaliplatin when treated with CCL20 and blocking CCR6 with anti-CCR6 improves cytotoxic effect of 5-Fluorouracil and Oxaliplatin. Poor response to chemotherapeutic after CCR6 activation was primarily due to activation molecular and cellular phenotypes and alteration in cell cycle. In conclusion, our data suggest that CCR6/CCL20 promotes colon cancer progression and CCR6-mediates signals contributed to poor response to conventional therapeutic such as 5-Fluorouracil and Oxaliplatin. Hence, targeting CCR6 in early stage will prevent metastasis, enhance therapeutic efficacy and reduce toxicity and will be a promising approach to improve clinical outcome. Citation Format: Briana A. Brock, Shailesh Singh, Hina A. Mir. Role of CCR6-CCL20 chemokine axis in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2990.