Abstract 1529: Colon cancer cells activate CCL20 and IL10 signaling to combat effects of 5 fluorouracil

Abstract Advances in screening and therapy have significantly decreased colon cancer mortality rates; however, predictions indicate that by 2030, approximately one million patients may still die from this disease each year. While chemotherapies are effective, cancer cells often develop resistance mechanisms that necessitate higher doses, which can lead to severe toxicities that hinder treatment effectiveness and pose additional health risks for patients. Depending on the stage of cancer, 5FU, an antimetabolite, is typically administered alone or in combination with oxaliplatin. Despite its cytotoxic properties, 5FU can induce inflammation in the colon, which may counteract its effectiveness against cancer. This inflammation, characterized by altered cytokine profile, contributes to the resilience of cancer cells. The focus of our study is on the proinflammatory chemokine CCL20, which is elevated during colon cancer, and plays a significant role in liver metastasis. CCL20 signaling is linked to epithelial to mesenchymal transition and can influence the efficacy of chemotherapy. Our research findings indicate that colon cancer cells treated with cytotoxic doses of 5FU show a notable increase in CCL20 secretion, as well as elevated levels of extracellular fatty acids compared to untreated cells. Furthermore, treatment with palmitic acid enhances CCL20 secretion. After 5FU treatment, there is also an increase in interleukin 10 (IL10). Interestingly, inhibiting CCL20 signaling, either by neutralizing CCL20 or blocking its receptor CCR6, further elevates IL10 levels. This suggests that colon cancer cells increase their tolerance to 5FU by raising CCL20 and IL10.Our study highlights the need for further investigation into these mechanisms to develop more effective treatment strategies that maintain or improve patients' quality of life. Citation Format: Janani Muralidharan, Shailesh Singh, Hina Mir. Colon cancer cells activate CCL20 and IL10 signaling to combat effects of 5 fluorouracil [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1529.