Cancer Immunology, Immunotherapy

, Volume 58, Issue 6, pp 877–886

The immunosuppressive tumor microenvironment in hepatocellular carcinoma

  • Yan-Li Pang
  • Hua-Gang Zhang
  • Ji-Run Peng
  • Xue-Wen Pang
  • Shu Yu
  • Qiao Xing
  • Xin Yu
  • Lei Gong
  • Yan-Hui Yin
  • Yu Zhang
  • Wei-Feng Chen
Original Article

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 

Abbreviations

APC

Antigen presenting cell

CTL

Cytotoxic T lymphocyte

HCC

Hepatocellular carcinoma

NIL

Non-tumor infiltrating lymphocyte

TAA

Tumor-associated antigen

TIL

Tumor infiltrating lymphocyte

Treg

Regulatory T cell

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Yan-Li Pang
    • 1
  • Hua-Gang Zhang
    • 1
  • Ji-Run Peng
    • 2
  • Xue-Wen Pang
    • 1
  • Shu Yu
    • 1
  • Qiao Xing
    • 1
  • Xin Yu
    • 2
  • Lei Gong
    • 2
  • Yan-Hui Yin
    • 1
  • Yu Zhang
    • 1
  • Wei-Feng Chen
    • 1
  1. 1.Department of ImmunologyPeking University Health Science CenterBeijingPeople’s Republic of China
  2. 2.Center of Hepatobiliary Surgery, People’s HospitalPeking University Health Science CenterBeijingPeople’s Republic of China

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