Abstract A020: TLR10 as a key innate immune effector regulating metabolic and redox homeostasis in head and neck squamous cell carcinoma

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly aggressive malignancy originating from the mucosal epithelium. While several Toll-like receptors (TLRs) are known to influence tumor behavior, the role of TLR10 in innate immune regulation within the tumor context remains poorly defined. In this study, I generated TLR10-deficient HNSCC cell lines using CRISPR/Cas9 to investigate its functional significance. Loss of TLR10 impaired cell viability and proliferation, suppressed cell cycle regulators (Cyclin A, Cyclin B, CDK2), and disrupted metabolic activity, as evidenced by decreased glycolysis (reduced ECAR, HK2, LDHA, PKM2) and lactate production. Additionally, TLR10-deficient cells showed elevated ROS levels and reduced antioxidant enzyme expression (SOD2, PRDX3, PRDX5, GPX4), suggesting disruption in redox homeostasis. These findings establish TLR10 as a novel innate immune effector that modulates cellular metabolism and redox balance in HNSCC, and may serve as a potential therapeutic target. Citation Format: Bokyung Joo, Hyeon Ji Kim, Hyo-Jin Song. TLR10 as a key innate immune effector regulating metabolic and redox homeostasis in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr A020.