Abstract 4530: mTOR inhibition augments antitumor T cell response by modulating the expression of immune regulatory molecules

Abstract The mechanistic target of rapamycin (mTOR) is a protein kinase that plays a critical role in regulating immune responses by modulating the growth, differentiation, activation and migration of various immune cells. Dysregulation of mTOR signaling, which is common in various cancers, can potentially disrupt the immune cell function, leading to weakened immune surveillance. This study evaluates the antitumor activity of an mTOR inhibitor drug, everolimus, focusing on its impact on antitumor immunity. Treatment with everolimus inhibited the growth of PD-1 resistant and poorly immunogenic ROC-1 syngeneic grafts, potentially through the activation of T cell-mediated immunity. Flow cytometry analysis of single cell suspension of tumor cells revealed increased CD8+ T cell infiltration and increased expression of class-I MHC in tumor cells in mice treated with everolimus when compared to vehicle. Moreover, everolimus reduced the number of exhausted (PD1+) CD4+, CD8+ T cells in tumors, indicating a more potent immune response against the cancer cells. The CD8+ tumor infiltrated lymphocytes (TILs) magnetically sorted and cocultured with the tumor cells showed significantly higher T cell cytotoxicity for the group of mice who received everolimus in comparison to vehicle. These findings suggest the potential of everolimus in boosting anti-tumor immunity, providing a rationale for further investigation. Citation Format: Priyatosh Nath, Alok Khandelwal, Ivan Alvarez, Chun Li, Srivatsa Vasudevan, Tara Moore-Medlin, Cherie-Ann Nathan. mTOR inhibition augments antitumor T cell response by modulating the expression of immune regulatory molecules [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 4530.