HBV-specific CD8 T cells present higher TNF α expression but lower cytotoxicity in hepatocellular carcinoma.

HBV-specific CD8 T cells present higher TNFα expression but lower cytotoxicity in hepatocellular carcinoma. Clin Exp Immunol. 2020 May 31;: Authors: Zhao L, Jin Y, Yang C, Li C Abstract TNFα is largely regarded as a proinflammatory cytokine, but several recent researches demonstrated that TNFα could possess immunoregulatory roles with potential to suppress antitumor immunity. Chronic hepatitis B virus (HBV) infection is a major risk factor of hepatocellular carcinoma (HCC) and HBV-specific CD8 T cells could exert antitumor roles in HCC patients. Here, we found that HBV-specific CD8 T cells, both in the peripheral blood and in the tumor microenvironment, were more enriched with TNFα-expressing cells than IFNγ-expressing cells. Compared to IFNγ-expressing HBV-specific CD8 T cells, TNFα-expressing HBV-specific CD8 T cells presented lower expression of inhibitory checkpoint molecules, including PD-1, TIM-3, and CTLA-4. HBV-specific CD8 T cells could mediate the lysis of autologous primary tumor cells and the inhibition of TNFα could further elevate their cytotoxic capacity. Subsequently, we demonstrated that TNFα inhibition in HBV-specific CD8 T cells could significantly increase granzyme B (GZMB) and perforin 1 (PRF1) expression while having no effect toward granzyme A (GZMA) expression. The addition of exogenous TNFα at low levels had no consistent effect on the expression of GZMA, GZMB, and PRF1, but at higher levels, exogen...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research