Original Article

Cancer Immunology, Immunotherapy

, Volume 58, Issue 6, pp 877-886

The immunosuppressive tumor microenvironment in hepatocellular carcinoma

  • Yan-Li PangAffiliated withDepartment of Immunology, Peking University Health Science Center
  • , Hua-Gang ZhangAffiliated withDepartment of Immunology, Peking University Health Science Center
  • , Ji-Run PengAffiliated withCenter of Hepatobiliary Surgery, People’s Hospital, Peking University Health Science Center
  • , Xue-Wen PangAffiliated withDepartment of Immunology, Peking University Health Science Center
  • , Shu YuAffiliated withDepartment of Immunology, Peking University Health Science Center
  • , Qiao XingAffiliated withDepartment of Immunology, Peking University Health Science Center
  • , Xin YuAffiliated withCenter of Hepatobiliary Surgery, People’s Hospital, Peking University Health Science Center
  • , Lei GongAffiliated withCenter of Hepatobiliary Surgery, People’s Hospital, Peking University Health Science Center
  • , Yan-Hui YinAffiliated withDepartment of Immunology, Peking University Health Science Center
    • , Yu ZhangAffiliated withDepartment of Immunology, Peking University Health Science Center Email author 
    • , Wei-Feng ChenAffiliated withDepartment of Immunology, Peking University Health Science Center Email author 

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Abstract

Increasing evidence indicates the immunosuppressive nature of the local environment in tumor. The present study was focused on analyzing the immune status within hepatocellular carcinoma. In contrast to the increasing number of CD4+ T cells, CD8+, CD3CD56+, CD3+CD56+, and γδT cells were all found to be under-represented in tumor infiltrating lymphocytes. Notably, the relative abundance of CD3+CD56+ cells appeared to be correlated with patient survival. Functional analysis demonstrated that CD4+ cells in the tumor tended to produce more IL-10 but less IFN-γ, whereas CD8+ cells showed impaired capacity for the production of both IFN-γ and perforin. Consistent with previous reports, we observed a significant increase of Foxp3+ cells in the tumor tissue. Intriguingly, although over 90% of CD4+CD25high cells were found to be Foxp3+, the majority of Foxp3+ cells were identified in the CD4+CD25medium and CD4+CD25 subsets. In support of its role as a negative regulator, CD4+CD25high cells suppressed the proliferation of CD4+CD25 cells isolated from the same tissues in an APC dependent manner. In conclusion, the tumor microenvironment of hepatocellular carcinoma is featured by the presence of multiple immunosuppressive factors.

Keywords

Tumor infiltrating lymphocytes Immunosuppressive factors Foxp3+ cells Tumor microenvironment Hepatocellular carcinoma