Abstract 4887: TIM-3 signaling modulates brain tumor growth in an orthotopic mouse model

T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is a transmembrane protein originally identified as a T helper type 1 (Th1)-specific protein. While there is growing interest in the roles of diseases, including tumors, the properties of TIM-3 in brain tumors remain unexplored. In this study, we investigated the functional properties of TIM-3 in the brain tumor microenvironment using TIM-3 mutant mice with intracellular signaling defects (Tim-3mut). To determine whether defects in TIM-3 signaling could affect brain tumor, we examined tumor growth using an intracranial mouse brain tumor model with glioma. EGFP-GL26 glioma cells were injected into the right hemisphere of mice with Tim-3mut mice and WT mice, and tumor growth was monitored using MRI. Interestingly, TIM-3 singling defects lead to reduced glioma growth and improved survival in the orthotopic mouse glioma model. Next, we performed experiments to investigate how TIM-3 signaling defects influence brain tumor growth and identified alterations in several signaling molecules, including CBP35, a lectin family member in Tim-3mut mice with GL26 tumor cells. Collectively, Our findings suggest that modulating TIM-3 signaling affects the brain tumor microenvironment, thereby influencing tumor growth and survival. Citation Format: Su Bin Won, Hyung-Seok Kim, Dae Yeon Kim, Ki Sun Kim, Su Jeong Gu, Chanju Lee, Hee Jung Yoon, Eun Jung Park. TIM-3 signaling modulates brain tumor growth in an orthotopic mouse model [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 4887.