TY - JOUR
T1 - CXCR5+CD8+ T cells are a distinct functional subset with an antitumor activity
AU - Chu, Fuliang
AU - Li, Haiyan S.
AU - Liu, Xindong
AU - Cao, Jingjing
AU - Ma, Wencai
AU - Ma, Ying
AU - Weng, Jinsheng
AU - Zhu, Zheng
AU - Cheng, Xiaoyun
AU - Wang, Zhiqiang
AU - Liu, Jingwei
AU - Jiang, Zi Yang
AU - Luong, Amber U.
AU - Peng, Weiyi
AU - Wang, Jing
AU - Balakrishnan, Kumudha
AU - Yee, Cassian
AU - Dong, Chen
AU - Davis, Richard Eric
AU - Watowich, Stephanie S.
AU - Neelapu, Sattva S.
N1 - Publisher Copyright:
© 2019, Springer Nature Limited.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41375-019-0464-2
DO - 10.1038/s41375-019-0464-2
M3 - Article
C2 - 31028278
AN - SCOPUS:85065176694
SN - 0887-6924
VL - 33
SP - 2640
EP - 2653
JO - Leukemia
JF - Leukemia
IS - 11
ER -