Abstract 922: Mutant KRAS enhances immune evasion via epitranscriptomic regulation of NT5E in colon cancer

Abstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Mutation in KRAS occurred in approximately 40% of patients, and leading to resistance to FDA approved anti-EGFR agents. Also, CRC patients harboring KRAS mutations do not respond well to immune checkpoint blockades. Therefore, additional therapeutic strategies to overcome KRAS mutations are strongly required. In recent years, N6-methyladenosine (m6A) modification on mRNA has been recognized for its significance in various cancer phenotype. This modification plays a crucial role not only in cancer cell behavior but also in shaping the tumor microenvironment (TME). Many studies about m6A in cancer focus on the direct roles and effects of m6A regulators. These regulators include writers, which attach m6A to RNA; erasers, which remove it; and readers, which bind to m6A to regulate the fate of mRNA. However, how oncogenic mutations affect the landscape of m6A deposition remains poorly understood. To explore the impact of KRAS mutations on m6A modifications, we performed MeRIP-seq and discovered significant changes, particularly in NT5E/CD73, a molecule known for its immune suppressive role in the TME. Our result suggest the potential for developing novel therapies by modulating the KRAS-m6A-NT5E axis in KRAS-mutated colorectal cancer. Citation Format: Seungjae Shin, Yoojin Yang, Sung-yup Cho. Mutant KRAS enhances immune evasion via epitranscriptomic regulation of NT5E in colon cancer. [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 922.