Abstract 4873: Characteristics of TIM-3 in regulating T cell activity in the brain tumor microenvironment

Abstract T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3), a member of TIM family, has been shown to exhibit diverse characteristics in a context-dependent manner. In this study, we investigated the characteristics of TIM-3 on T cells in the brain tumor microenvironment. First, using an intracranial syngeneic mouse model, we examined the expression of TIM-3 in the brain tumor microenvironment. Immunohistochemistry (IHC) revealed that TIM-3 as well as PD-1 was expressed on various cell types, including CD3-positive cells in brain sections of tumor-bearing mice. Similar expression patterns were observed in tumor-infiltrating lymphocytes (TILs) by using flow cytometry analysis. To investigate the role of TIM-3 in T cells within the brain tumor microenvironment, we utilized T-lymphocyte specific TIM-3 conditional knock-out (TIM-3fl/fl Lck-cre, TIM-3 cKO). TIM-3 cKO mice exhibit a higher CD8+/CD4+ TIL ratio in the ipsilateral brain regions compared to tumor-bearing wild-type (WT) mice after GL26 cell injection into the right hemisphere. Moreover, in-vivo experiments with TILs demonstrated the influence of TIM-3 on T cell functional activity within the brain tumor microenvironment. Collectively, these results suggest that TIM-3 of T cells have an influence on the immune microenvironment of brain tumors. Citation Format: mingi song, Su Bin Won, Hyung-Seok Kim, Dae Yeon Kim, Ki Sun Kim, Su Jeong Gu, Chanju Lee, Hee Jung Yoon, Eun Jung Park. Characteristics of TIM-3 in regulating T cell activity in the brain tumor microenvironment [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 4873.