The immunosuppressive tumor microenvironment in hepatocellular carcinoma |
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Authors: | 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 |
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Institution: | (1) Department of Immunology, Peking University Health Science Center, 38 Xue Yuan Road, 100191 Beijing, People’s Republic of China;(2) Center of Hepatobiliary Surgery, People’s Hospital, Peking University Health Science Center, 42 Beilishilu, 100044 Beijing, People’s Republic of China |
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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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Keywords: | Tumor infiltrating lymphocytes Immunosuppressive factors Foxp3+ cells Tumor microenvironment Hepatocellular carcinoma |
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