Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients

Authors

  • Jia Zhou,

    1. State Key Laboratory of Biocontrol, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
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  • Tong Ding,

    1. State Key Laboratory of Biocontrol, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
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  • Weidong Pan,

    1. Department of Hepatobiliary Surgery, the Third Affiliated Hospital, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
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  • Ling-yan Zhu,

    1. State Key Laboratory of Biocontrol, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
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  • Lian Li,

    Corresponding author
    1. State Key Laboratory of Biocontrol, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
    • College of Life Science, Sun Yat-sen (Zhongshan) University, Guangzhou 510275, People's Republic of China
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  • Limin Zheng

    1. State Key Laboratory of Biocontrol, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
    2. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China
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Abstract

Immunosuppression mediated by regulatory T cells (Tregs) is a key facilitator of tumor immune evasion, but the source of these Tregs and their contribution to human cancer progression remains unclear. This study investigated the properties of FoxP3+ Tregs, their prognostic value in patients with hepatocellular carcinoma (HCC) and the underlying mechanisms of FoxP3+ Treg intratumoral accumulation. In addition to an increased number of circulating FoxP3+ Tregs, the results also showed that FoxP3+ Tregs gathered in the tumor site, where they suppressed tissue-derived CD4+CD25 T-cell activation (p < 0.001), promoting disease progression and poor prognosis in HCC patients (< 0.01). The intratumoral prevalence of FoxP3+ Tregs was associated with a high density of macrophages (Mφ) (p < 0.001). Depletion of tissue Mφ thus attenuated the increase of liver FoxP3+ Treg frequency attributed to in vivo inoculation with hepatoma (p = 0.01), whereas Mφ exposed to tumor culture supernatants from hepatoma-derived cell lines increased FoxP3+ Treg frequency in vitro (p < 0.001). This increase was partially blocked by antiinterleukin-10 antibody (p < 0.01). In conclusion, tumor-associated Mφ may trigger a rise of the intratumoral FoxP3+ Treg population, which in turn may promote HCC progression. © 2009 UICC

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