CXCR5+ CD8+ T cells could induce the death of tumor cells in HBV-related hepatocellular carcinoma

- CXCR5+ CD8+ T cells showed elevated PD-1 but reduced Tim-3 and CTLA-4 expression.
- CXCR5+ CD8+ T cells showed higher proliferation, especially after PD-1 blockade.
- CXCR5+ CD8+ T cells showed higher granzyme B synthesis and release.
- Tumor cells were more readily eliminated by CXCR5+ CD8+ T cells.
- B cells were resistant to CXCR5+ CD8+ T cell-mediated killing through IL-10.

The follicular CXCR5+ CD8+ T cells have recently emerged as a critical cell type in mediating peripheral tolerance as well as antiviral immune responses during chronic infections. In this study, we investigated the function of CXCR5+ CD8+ T cells in HBV-related hepatocellular carcinoma patients. Compared to CXCR5− CD8+ T cells, CXCR5+ CD8+ T cells presented elevated PD-1 expression but reduced Tim-3 and CTLA-4 expression. Upon anti-CD3/CD28 stimulation, CXCR5+ CD8+ T cells demonstrated higher proliferation potency than CXCR5− CD8+ T cells, especially after PD-1 blockade. CXCR5+ CD8+ T cells also demonstrated significantly higher granzyme B synthesis and release, as well as higher level of degranulation. Tumor cells were more readily eliminated by CXCR5+ CD8+ T cells than by CXCR5− CD8+ T cells. Interestingly, we found that B cells were more resistant to CXCR5+ CD8+ T cell-mediated killing than tumor cells, possibly through IL-10-mediated protection. In addition, the CXCR5+ CD8+ T cell-mediated cytotoxic effects on tumor cells could be significantly enhanced by PD-L1 blockade. Together, we presented that in patients with in HBV-related hepatocellular carcinoma, CXCR5+ CD8+ T cells could mediate tumor cell death more potently than the CXCR5− CD8+ T cells in vitro while the autologous B cells were protected.