Adoptive transfer of IL-4 reprogrammed Tc17 cells elicits anti-tumor immunity through functional plasticity

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Title:	Adoptive transfer of IL-4 reprogrammed Tc17 cells elicits anti-tumor immunity through functional plasticity
Authors:	Chiung-Hui, L;Liu, Chiung-Hui;Lin, Bo-Shiou;Lin, Bo-Shiou;吳美瑤;Wu, Mei-Yao;宋瑛琪;Song, Ying-Chyi;柯道維;Ke, Tao-Wei;Chou, Yu-Lun;Chou, Yu-Lun;劉傳騰;Liu, Chuan-Teng;Li, Chia-Hsin;Lin, Chia-Hsin;Radoj, Vedran;Radojcic, Vedran;Drak, Charles;Drake, Charles;顏宏融
Contributors:	醫學暨健康學院醫學檢驗暨生物技術學系
Keywords:	Eomes;IL-17;IL-4;T cell reprogramming;Tc17;Trat1;adoptive cell therapy.
Date:	2022-07-01
Issue Date:	2023-03-29 02:03:46 (UTC+0)
Publisher:	亞洲大學
Abstract:	Ability of IL-17-producing CD8+ T cells (Tc17) to transform into cytotoxic anti-tumour effectors makes them a promising candidate for immune effector cell (IEC) therapy. However, key factors regulating Tc17 reprogramming remain poorly defined, hindering translation of Tc17-based IEC use from bench to bedside. We probed the effects of multiple cytokines and underlying signalling pathways on Tc17 cells and identified pivotal role for IL-4 and PI3K/AKT in promoting Tc17 transformation into cytotoxic IFN-γ-producing IECs, an effect dependent on Eomes expression. IL-4 not only triggered Tc17 cytotoxicity, but also induced cell expansion, which significantly improved the antitumour potential of Tc17 cells compared to that of IFN-γ-producing CD8+ T cells (Tc1) in a murine model. Furthermore, IL-4/AKT signalling drove the upregulation of the T-cell receptor-associated transmembrane adaptor 1 (Trat1) in Tc17 cells to promote IL-4-induced T-cell receptor stabilization and Tc17 cytotoxicity. Finally, we proposed a possible procedure to expand human Tc17 from peripheral blood of cancer patients, and confirmed the function of IL-4 in Tc17 reprogramming. Collectively, these results document a novel IL-4/AKT/Eomes/Trat1 axis that promotes expansion and transformation of Tc17 cells into cytotoxic effectors with a therapeutic potential. IL-4 priming of Tc17 cells should be further explored as a cell therapy engineering strategy to generate IECs to augment anti-tumour responses.
Appears in Collections:	[Department of Biotechnology] Journal Article

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