Reactivity toward Bifidobacterium longum and Enterococcus hirae demonstrate robust CD8+ T cell response and better prognosis in HBV-related hepatocellular carcinoma.

Recent studies suggest that several bacterial species are involved in tumor immunosurveillance and antitumor immunity. The role of bacteria in immune responses in HBV-related hepatocellular carcinoma (HCC) patients is still unknown. In this study, we examined the bacteria-reactive CD8 + T cell response in patients with HBV-related HCC. We found that circulating CD8 + T cells from healthy individuals demonstrated minimal or zero specificity toward a series of commensals and bacteria previously associated with antitumor effects, including Escherichia coli , Enterococcus faecium , Bifidobacterium longum , Bacteroides fragilis , and Enterococcus hirae . In contrast, the circulating CD8 + T cells from HBV-related HCC patients presented significantly elevated bacteria-reactive responses, albeit with high variations among different HCC individuals. Reactivity toward bacteria was also identified in tumor-infiltrating CD8 + T cells. These bacteria-reactive responses were not primarily induced by TLR ligand, but were dependent on the presence of antigen-presenting monocytes, and were MHC class I-restricted. Interestingly, we observed that the CD8 + T cell-to-Foxp3 + regulatory T cell ratio was positively correlated with the proportions of Bifidobacterium longum -reactive and Enterococcus hirae -reactive CD8 + T cells, while the frequency of PD-1 + CD8 + T cells was negatively correlated with the frequency of Enterococcus hirae -reactive CD8 + T cells. Furthermore, the disease-free survival time of HCC patients after tumor resection was positively correlated with the frequencies of Bifidobacterium longum -reactive and Enterococcus hirae -reactive CD8 + T cells. Together, these results suggested that certain bacterial species might present valuable antitumor effects. [ABSTRACT FROM AUTHOR]