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

Immunosuppression mediated by regulatory T cells (Trees) 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(+) Tree intratumoral accumulation. In addition to an increased number of circulating FoxP3(+) Tregs, the results also showed that FoxP3(+) Trees 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 (M phi) (p < 0.001). Depletion of tissue M phi thus attenuated the increase of liver FoxP3(+) Tree frequency attributed to in vivo inoculation with hepatoma (p = 0.01), whereas M phi 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 M phi may trigger a rise of the intratumoral FoxP3(+) Tree population, which in turn may promote HCC progression. (C) 2009 UICC