Abstract 381: Inhibition of CCR6-CCL20 axis enhances cytotoxic effect of chemotherapeutics in colon cancer

Abstract

Abstract Response of chemotherapeutic offered to treat colon cancer are often short-lived due to chemoresistance and severe toxicity associated with the therapy. Hence, development of less toxic treatment options is imperative to improve efficacy and therapeutic outcome. We have shown that chemokine CCR6 and its natural ligand is expressed in colon cancer and correlates with advanced disease. Aim of this study was to establish the association of CCCR6/CCL26 signaling axis on development of chemoresistance and chemotherapeutic response. Our data shows higher expression of receptor, poor cytotoxic effect of 5-Fluorouracil (5-FU) when cells are treated with CCL20 while better response to 5-FU when CCR6 signaling is blocked using anti-CCR6 monoclonal antibody. The observed differences in the cytotoxic effects of 5-FU could be primarily due to CCR6-mediated alteration of cell cycle, activation of cell survival and anti-apoptotic signaling. Further investigations in a preclinical model will rationalize developing CCR6 directed therapies to improve response to conventional chemotherapeutics and offer less toxic treatment options to colon cancer patients. Citation Format: Hina Mir, Shailesh Singh. Inhibition of CCR6-CCL20 axis enhances cytotoxic effect of chemotherapeutics in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 381.