Th9 Cells Represent a Unique Subset of CD4(+) T Cells Endowed with the Ability to Eradicate Advanced Tumors

Lu Yong; Wang Qiang; Xue Gang; Bi Enguang; Ma Xingzhe; Wang Aibo; Qian Jianfei; Dong Chen; Yi Qing

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Th9 Cells Represent a Unique Subset of CD4(+) T Cells Endowed with the Ability to Eradicate Advanced Tumors

机译：TH9细胞代表CD4（+）T细胞的独特子集，赋予了根除晚期肿瘤的能力

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The antitumor effector T helper 1 (Th1) and Th17 cells represent two T cell paradigms: short-lived cytolytic Th1 cells and "stem cell-like'' memory Th17 cells. We report that Th9 cells represent a third paradigmthey are less-exhausted, fully cytolytic, and hyperproliferative. Only tumor-specific Th9 cells completely eradicated advanced tumors, maintained a mature effector cell signature with cytolytic activity as strong as Th1 cells, and persisted as long as Th17 cells in vivo. Th9 cells displayed a unique Pu. 1-Traf6-NF-kappa B activation-driven hyperproliferative feature, suggesting a persistence mechanism rather than an antiapoptotic strategy. Th9 antitumor efficacy depended on interleukin-9 and upregulated expression of Eomes and Traf6. Thus, tumor-specific Th9 cells are a more effective CD4(+) T cell subset for adoptive cancer therapy.

机译：抗肿瘤效应器T辅助辅助辅助剂1（TH1）和TH17细胞代表两种T细胞范式：短寿命的细胞分解TH1细胞和“干细胞状”记忆TH17细胞。我们报告说TH9细胞代表第三个PARADIGMTHEY少耗尽，完全cytolytic，且过度增殖性。只有肿瘤特异性Th9细胞完全消除先进的肿瘤，将具有Cytolytic活性的成熟效应细胞特征与Th1细胞具有强，并且只要体内的Th17细胞持续存在。1 -Traf6-NF-Kappa B激活驱动的过度增强特征，表明持久性机制而不是抗污染策略。TH9抗肿瘤功效依赖于白细胞介素-9和eomes和TRAF6的上调表达。因此，肿瘤特异性TH9细胞是更有效的 CD4（+）T细胞子集，用于收养癌症疗法。

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《Cancer Cell》 |2018年第6期|共20页
作者
Lu Yong; Wang Qiang; Xue Gang; Bi Enguang; Ma Xingzhe; Wang Aibo; Qian Jianfei; Dong Chen; Yi Qing;
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作者单位

Wake Forest Sch Med Dept Microbiol &

Immunol Winston Salem NC 27101 USA;

Cleveland Clin Lerner Res Inst Dept Canc Biol Cleveland OH 44195 USA;

Wake Forest Sch Med Dept Microbiol &

Immunol Winston Salem NC 27101 USA;

Cleveland Clin Lerner Res Inst Dept Canc Biol Cleveland OH 44195 USA;

Cleveland Clin Lerner Res Inst Dept Canc Biol Cleveland OH 44195 USA;

Tsinghua Univ Inst Immunol Beijing 100084 Peoples R China;

Cleveland Clin Lerner Res Inst Dept Canc Biol Cleveland OH 44195 USA;

Tsinghua Univ Inst Immunol Beijing 100084 Peoples R China;

Cleveland Clin Lerner Res Inst Dept Canc Biol Cleveland OH 44195 USA;

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正文语种 eng
中图分类肿瘤学;
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专利

1. Th9 Cells Represent a Unique Subset of CD4(+) T Cells Endowed with the Ability to Eradicate Advanced Tumors [J] . Lu Yong, Wang Qiang, Xue Gang, Cancer Cell . 2018,第6期

机译：TH9细胞代表CD4（+）T细胞的独特子集，赋予了消除高级肿瘤的能力
2. TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia [J] . Kemal Catakovic, Franz Josef Gassner, Christoph Ratswohl, Oncoimmunology. . 2018,第1期

机译：表达CD4 + T细胞的TIGIT代表慢性淋巴细胞白血病中的肿瘤 - 支持性T细胞亚血症
3. Interferon-gamma and tumor necrosis factor-alpha promote the ability of human placenta-derived mesenchymal stromal cells to express programmed death ligand-2 and induce the differentiation of CD4(+)interleukin-10(+) and CD8(+)interleukin-10(+)Treg subsets [J] . Li Heng, Wang Weiwei, Wang Guoyan, Cytotherapy . 2015,第11期

机译：干扰素-γ和肿瘤坏死因子-α促进人类胎盘来源的间充质基质细胞表达程序性死亡配体2并诱导CD4（+）interleukin-10（+）和CD8（+）interleukin-10分化。（+）Treg子集
4. CD40-ACTIVATED B (CD40-B) CELLS LOADED WITH AUTOLOGOUS TUMOR RNA AS A NOVEL ANTIGEN-PRESENTING CELL VACCINE FOR CANINE LYMPHOMA [C] . Amy LaBlanc, Erika L Krick, Beth Overley, Annual conference of the Veterinary Cancer Society . 2008

机译：CD40-活化的B（CD40-B）用自体肿瘤RNA负载，作为犬淋巴瘤的新型抗原呈递细胞疫苗
5. CD4+T cell effector and regulatory subsets involved in rescuing facial motoneurons from axotomy -induced cell death. [D] . DeBoy, Cynthia Ann. 2005

机译：CD4 + T细胞效应子和调节子集涉及从轴切术诱导的细胞死亡中拯救面部运动神经元。
6. Th9 Cells Represent a Unique Subset of CD4+ T Cells Endowed with the Ability to Eradicate Advanced Tumors [O] . Yong Lu, Qiang Wang, Gang Xue, -1

机译：Th9细胞代表具有根除晚期肿瘤能力的CD4 + T细胞的独特子集
7. The CD7− T cell subset represents the majority of IL-5-secreting cells within CD4+CD45RA− T cells [O] . REINHOLD, U, LIU, L, SESTERHENN, J, 1996

机译：CD7-T细胞亚群代表CD4 + CD45RA- T细胞中大多数IL-5分泌细胞
8. Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T-Cells Secreting an Engineered Tumor-Specific Immunotoxin [R] . Yotnda, P. 2010

机译：通过肿瘤特异性细胞毒性T细胞分泌工程化肿瘤特异性免疫毒素，增强根除淋巴瘤

Th9 Cells Represent a Unique Subset of CD4(+) T Cells Endowed with the Ability to Eradicate Advanced Tumors

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