Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients.
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 (Mvarphi) (p < 0.001). Depletion of tissue Mvarphi thus attenuated the increase of liver FoxP3(+) Treg frequency attributed to in vivo inoculation with hepatoma (p = 0.01), whereas Mvarphi 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 Mvarphi may trigger a rise of the intratumoral FoxP3(+) Treg population, which in turn may promote HCC progression.
Zhou
Jia
J
State Key Laboratory of Biocontrol, Sun Yat-Sen (Zhongshan) University, Guangzhou, People's Republic of China.
Ding
Tong
T
Pan
Weidong
W
Zhu
Ling-Yan
LY
Li
Lian
L
Zheng
Limin
L
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000276:immunology* / Q000401:mortality; D008264:Macrophages / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors