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The immunosuppressive tumor microenvironment in hepatocellular carcinoma

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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+, CD3−CD56+, 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.

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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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Acknowledgments

The work received supports from the Beijing Municipal Government Foundation for Natural Sciences (7071006 and 7061003) and the National 863 High Technology Program of China (2006AA02Z486).

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Authors and Affiliations

  1. Department of Immunology, Peking University Health Science Center, 38 Xue Yuan Road, 100191, Beijing, People’s Republic of China

    Yan-Li Pang, Hua-Gang Zhang, Xue-Wen Pang, Shu Yu, Qiao Xing, Yan-Hui Yin, Yu Zhang & Wei-Feng Chen

  2. Center of Hepatobiliary Surgery, People’s Hospital, Peking University Health Science Center, 42 Beilishilu, 100044, Beijing, People’s Republic of China

    Ji-Run Peng, Xin Yu & Lei Gong

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  1. Yan-Li Pang
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  2. Hua-Gang Zhang
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Correspondence to Yu Zhang or Wei-Feng Chen.

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Pang, YL., Zhang, HG., Peng, JR. et al. The immunosuppressive tumor microenvironment in hepatocellular carcinoma. Cancer Immunol Immunother 58, 877–886 (2009). https://doi.org/10.1007/s00262-008-0603-5

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