CXCR5+CD8+ T cells are a distinct functional subset with an antitumor activity.
Fuliang ChuHaiyan S LiXindong LiuJingjing CaoWencai MaYing MaJinsheng WengZheng ZhuXiaoyun ChengZhiqiang WangJingwei LiuZi Yang JiangAmber U LuongWeiyi PengJing WangKumudha BalakrishnanCassian YeeChen DongRichard Eric DavisStephanie S WatowichSattva S NeelapuPublished in: Leukemia (2019)
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.
Keyphrases
- cell migration
- end stage renal disease
- rna seq
- single cell
- chronic kidney disease
- newly diagnosed
- induced apoptosis
- peritoneal dialysis
- endothelial cells
- prognostic factors
- gene expression
- genome wide
- cell cycle arrest
- diffuse large b cell lymphoma
- transforming growth factor
- epithelial mesenchymal transition
- dendritic cells
- high glucose
- regulatory t cells
- drug induced
- dna methylation
- cell therapy
- anti inflammatory
- pi k akt