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

Publication date: Available online 8 July 2017
Source:Experimental Cell Research
Author(s): Yihui Rong, Zheng Dong, Zhixian Hong, Yun Jin, Wei Zhang, Bailong Zhang, Wei Mao, Huifang Kong, Chunping Wang, Bin Yang, Xudong Gao, Zhenyu Song, Susan E. Green, Haihan K. Song, Hongbo Wang, Yinying Lu
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.



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