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Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients
Author(s) -
Zhou Jia,
Ding Tong,
Pan Weidong,
Zhu Lingyan,
Li Lian,
Zheng Limin
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24556
Subject(s) - foxp3 , hepatocellular carcinoma , immunosuppression , cancer research , medicine , regulatory t cell , immune system , tumor progression , il 2 receptor , population , immunology , in vivo , cancer , t cell , biology , environmental health , microbiology and biotechnology
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