CXCR5(+)CD8(+) T cells are a distinct functional subset with 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 a 77-gene signature unique to CXCR5(+)CD8(+) T cells. The upregulated 33 genes among the 77-gene signature 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.