CXCR5+CD8+ T cells are a distinct functional subset with an antitumor activity

Fuliang Chu, Haiyan S. Li, Xindong Liu, Jingjing Cao, Wencai Ma, Ying Ma, Jinsheng Weng, Zheng Zhu, Xiaoyun Cheng, Zhiqiang Wang, Jingwei Liu, Zi Yang Jiang, Amber U. Luong, Weiyi Peng, Jing Wang, Kumudha Balakrishnan, Cassian Yee, Chen Dong, Richard Eric Davis, Stephanie S. WatowichSattva S. Neelapu

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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 CXCR5CD8+ 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.

Original languageEnglish (US)
Pages (from-to)2640-2653
Number of pages14
JournalLeukemia
Volume33
Issue number11
DOIs
StatePublished - Nov 1 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource
  • Biostatistics Resource Group
  • Flow Cytometry and Cellular Imaging Facility
  • Research Animal Support Facility
  • Advanced Microscopy Core

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