Abstract 4078: EZH2 marks polyfunctional memory T cells and controls tumor immunity
Polyfunctional T cells mediate potent anti-viral immunity. However, the nature and molecular mechanisms controlling their functional signature remain poorly understood. Here we report that polyfunctional T cells are characterized by high proliferative capacity and apoptotic resistance. Enhancer of z...
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Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.4078-4078 |
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Sprache: | eng |
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Zusammenfassung: | Polyfunctional T cells mediate potent anti-viral immunity. However, the nature and molecular mechanisms controlling their functional signature remain poorly understood. Here we report that polyfunctional T cells are characterized by high proliferative capacity and apoptotic resistance. Enhancer of zeste homolog 2 (EZH2) phenotypically marks them and functionally controls their survival and expansion. Notch signaling regulates effector T cell function. We show that EZH2 represses Numb and Fbxw7, two Notch repressors, activates Notch signaling, and Notch subsequently stimulates Bcl-2 expression and protects EZH2+ T cells from apoptosis via trimethylating histone H3 on lysine 27. Moreover, EZH2 targets T cell cycling repressors and promotes their expansion. EZH2+CD8+ T cells mediate anti-tumor immunity and are associated with improved long-term cancer survival. Together, the data reveal a novel role and mechanism for EZH2 in controlling polyfunctional T cells. Thus, manipulation of EZH2 signaling in T cells may have therapeutic potential in treating cancer patients.
Citation Format: Ende Zhao, Tomasz Maj, Ilona Kryczek, Lili Zhao, Shuang Wei, Shanshan Wan, Joel Crespo, Wojciech Szeliga, Linda Vatan, Ke Wu, Arul M. Chinnaiyan, Theodore H. Welling, Victor E. Marquez, Jan Kotarski, Yi Zhang, Rebecca Liu, Kaixiong Tao, Guobin Wang, Weiping Zou. EZH2 marks polyfunctional memory T cells and controls tumor immunity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4078. doi:10.1158/1538-7445.AM2014-4078 |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.AM2014-4078 |