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

• Published in: Experimental cell research 2017-09, Vol.358 (2), p.352-359
• Main Authors: Rong, Yihui, Dong, Zheng, Hong, Zhixian, Jin, Yun, Zhang, Wei, Zhang, Bailong, Mao, Wei, Kong, Huifang, Wang, Chunping, Yang, Bin, Gao, Xudong, Song, Zhenyu, Green, Susan E., Song, Haihan K., Wang, Hongbo, Lu, Yinying
• Format: Article
• Language: English
• Subjects: Bifidobacteriales Infections - immunology; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; CD8+ T cell; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Enterococcus hirae; Forkhead Transcription Factors - metabolism; Gram-Positive Bacterial Infections - immunology; HBV-related hepatocellular carcinoma; Hepatitis B virus; Humans; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Liver Neoplasms - virology; Microbiome; Prognosis; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - virology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2017.07.009

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.