Glial Tim-3 Shows Distinct Expression Patterns And Functions In Brain Tumor Microenvironment

Abstract T-cell immunoglobulin and mucin domain containing molecule-3 (TIM-3) is a transmembrane glycoprotein. TIM-3 has diverse immune functions, which differ according to the specific cell type and cell status and appears to play both positive and negative roles in a context-dependent manner. In this study, we questioned whether TIM-3 could be involved in immune surveillance against brain tumor, and thereby affect tumor immunity. To explore whether and how TIM-3 responds to brain tumor and whether it could play a role in specific immune cells of the brain tumor microenvironment, we used an intracranial mouse brain tumor model system. Here, we present that TIM-3 is expressed on both growing tumor cells and their surrounding cells including glial and T cells in an orthotopic mouse glioma model. Comparison of cells from tumor-bearing and contralateral hemispheres of a mouse glioma model shows that TIM-3 level is distinct in tumor-infiltrating CD45midCD11b+ glial cells. We find that TIM-3 affects the expression of several immune-associated molecules in primary glia-exposed conditioned media (CM) from brain tumors. Collectively, these findings suggest that glial TIM-3 actively and distinctively responds to brain tumor, and plays specific immunoregulatory roles in the brain tumor microenvironment.