Abstract
Abstract Although cancer burden in patients with advanced diseases results in T cell exhaustion and failed prior therapies, some of them achieved durable clinical responses to salvage therapy (chemotherapy or radiation therapy) implying a presence of tumor-reactive resilient T cells in them. However, the phenotype and functional features of resilient T cells have not been clearly defined. We found that CX3CR1+ CD8+ T cells with low mitochondrial membrane potential demonstrated features of resilient T cells: (a) their cytotoxic T cell function (degranulation/CD107a expression) recovered quickly after tumor burden has been reduced by radiation therapy or chemotherapy; (b) they maintain a low profile of glycolysis but produce optimal levels of ATP; (c) they express lower levels of PD-1 and TOX; (4) they share a feature of stem-like T cells (TCF1+PD-1+) that can be responsive to immunotherapy; (5) they avoid accumulation of a harmful level of cytosolic reactive oxygen species (ROS) that may cause T cell exhaustion; (6) they upregulate malic enzyme 1 (ME1) to balance glycolysis and ROS, and to expand cytotoxic effector T cells. These unique features of resilient T cells may not only be used as T cell biomarker to design rational combination therapy to control advanced cancers but can also be used to convey a resilient functional state to T cells in patients who lack them. Citation Format: Joanina K. Gicobi, Yiyi Yan, Hu Zeng, Sean Park, Haidong Dong. Characterization of cytotoxic resilient T cells in patients with advanced cancers in response to salvage radiation therapy or chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4160.
Published Version
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