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

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Yun Jin, Cuicui Lang, Jianzhong Tang, Jiawei Geng, Haihan K. Song, Zhiwei Sun, Jinfeng Wang
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.



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