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

CXCR5 mediates homing of both B and follicular helper T (T_FH) cells into follicles of secondary lymphoid organs. We found that CXCR5⁺CD8⁺ T cells are present in human tonsils and follicular lymphoma, inhibit T_FH-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 T_FH-mediated B cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.