Abstract IA14: mTOR as a central regulator of T-cell activation, differentiation, and function

Abstract

Abstract While the exquisite specificity of the T-cell receptor (TCR) MHC + peptide interaction heralds recognition, it is ultimately the cues from the immune microenvironment that dictate the outcome of this recognition. Our lab has proposed that mTOR plays a critical role in integrating signals and thus determining the outcome of antigen recognition. Indeed, we have demonstrated that mTORC1 and mTORC2 signaling can selectively guide CD4+ effector and regulatory T-cell differentiation and function as well as CD8+ effector and memory T-cell differentiation and function. Recent studies have revealed that mTOR performs this function in part by coordinating T-cell activation and function with metabolic reprogramming. Consequently, targeting downstream mTOR signaling and metabolism can promote T-cell effector function and persistence in order to enhance cancer immunotherapy. Likewise, targeting mTOR can inhibit T-effector function and promote the generation of regulatory T cells to treat autoimmune disease and prevent transplantation rejection. Citation Format: Jonathan Powell, Chirag Patel, Hong Sun, Michael Claiborne. mTOR as a central regulator of T-cell activation, differentiation, and function [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr IA14.