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CXCR5+CD8+ T cells are a distinct functional subset with an antitumor activity.
Leukemia ( IF 12.8 ) Pub Date : 2019-04-25 , DOI: 10.1038/s41375-019-0464-2 Fuliang Chu 1 , Haiyan S Li 2 , Xindong Liu 2, 3 , Jingjing Cao 1 , Wencai Ma 4 , Ying Ma 5 , Jinsheng Weng 1 , Zheng Zhu 3 , Xiaoyun Cheng 1 , Zhiqiang Wang 1 , Jingwei Liu 1 , Zi Yang Jiang 6 , Amber U Luong 6 , Weiyi Peng 5, 7 , Jing Wang 4 , Kumudha Balakrishnan 1 , Cassian Yee 5 , Chen Dong 2, 8 , Richard Eric Davis 1 , Stephanie S Watowich 2 , Sattva S Neelapu 1
Leukemia ( IF 12.8 ) Pub Date : 2019-04-25 , DOI: 10.1038/s41375-019-0464-2 Fuliang Chu 1 , Haiyan S Li 2 , Xindong Liu 2, 3 , Jingjing Cao 1 , Wencai Ma 4 , Ying Ma 5 , Jinsheng Weng 1 , Zheng Zhu 3 , Xiaoyun Cheng 1 , Zhiqiang Wang 1 , Jingwei Liu 1 , Zi Yang Jiang 6 , Amber U Luong 6 , Weiyi Peng 5, 7 , Jing Wang 4 , Kumudha Balakrishnan 1 , Cassian Yee 5 , Chen Dong 2, 8 , Richard Eric Davis 1 , Stephanie S Watowich 2 , Sattva S Neelapu 1
Affiliation
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CXCR5 mediates homing of both B and follicular helper T (TFH) cells into follicles of secondary lymphoid organs. We found that CXCR5+CD8+ T cells are present in human tonsils and follicular lymphoma, inhibit TFH-mediated B cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5+CD8+ T cells into an animal model of lymphoma resulted in significantly greater antitumor activity than CXCR5-CD8+ T cells. Furthermore, RNA-Seq-based transcriptional profiling revealed 77 differentially expressed genes unique to CXCR5+CD8+ T cells. Among these, a signature comprised of 33 upregulated genes correlated with improved survival in follicular lymphoma patients. We also showed that CXCR5+CD8+ T cells could be induced and expanded ex vivo using IL-23 plus TGF-β, suggesting a possible strategy to generate these cells for clinical application. In summary, our study identified CXCR5+CD8+ T cells as a distinct T cell subset with ability to suppress TFH-mediated B cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.
中文翻译：
CXCR5+CD8+ T 细胞是具有抗肿瘤活性的独特功能子集。
CXCR5 介导 B 细胞和滤泡辅助 T (TFH) 细胞归巢到次级淋巴器官的滤泡中。我们发现CXCR5+CD8+T细胞存在于人扁桃体和滤泡性淋巴瘤中，抑制TFH介导的B细胞分化，并表现出很强的细胞毒活性。与这些发现一致，将 CXCR5+CD8+T 细胞过继转移至淋巴瘤动物模型中，其抗肿瘤活性显着高于 CXCR5-CD8+T 细胞。此外，基于 RNA-Seq 的转录分析揭示了 CXCR5+CD8+ T 细胞特有的 77 个差异表达基因。其中，由 33 个上调基因组成的特征与滤泡性淋巴瘤患者生存率的提高相关。我们还表明，使用 IL-23 和 TGF-β 可以在体外诱导和扩增 CXCR5+CD8+ T 细胞，这表明产生这些细胞用于临床应用的可能策略。总之，我们的研究发现 CXCR5+CD8+ T 细胞是一种独特的 T 细胞亚群，能够抑制 TFH 介导的 B 细胞分化，发挥强大的抗肿瘤活性，并为滤泡性淋巴瘤患者带来良好的预后。
更新日期：2019-05-16
中文翻译：
CXCR5+CD8+ T 细胞是具有抗肿瘤活性的独特功能子集。
CXCR5 介导 B 细胞和滤泡辅助 T (TFH) 细胞归巢到次级淋巴器官的滤泡中。我们发现CXCR5+CD8+T细胞存在于人扁桃体和滤泡性淋巴瘤中，抑制TFH介导的B细胞分化，并表现出很强的细胞毒活性。与这些发现一致，将 CXCR5+CD8+T 细胞过继转移至淋巴瘤动物模型中，其抗肿瘤活性显着高于 CXCR5-CD8+T 细胞。此外，基于 RNA-Seq 的转录分析揭示了 CXCR5+CD8+ T 细胞特有的 77 个差异表达基因。其中，由 33 个上调基因组成的特征与滤泡性淋巴瘤患者生存率的提高相关。我们还表明，使用 IL-23 和 TGF-β 可以在体外诱导和扩增 CXCR5+CD8+ T 细胞，这表明产生这些细胞用于临床应用的可能策略。总之，我们的研究发现 CXCR5+CD8+ T 细胞是一种独特的 T 细胞亚群，能够抑制 TFH 介导的 B 细胞分化，发挥强大的抗肿瘤活性，并为滤泡性淋巴瘤患者带来良好的预后。
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