title: Identification of a FOXP3(+)CD3(+)CD56(+) population with immunosuppressive function in cancer tissues of human hepatocellular carcinoma.
abstract: The liver resident lymphoid population is featured by the presence of a large number of CD3(+)CD56(+) cells referred as natural T cells. In human hepatocellular carcinoma (HCC) patients, the natural T cells were found to be sharply decreased in tumor (5.871 ± 3.553%) versus non-tumor (14.02 ± 6.151%) tissues. More intriguingly, a substantial fraction of the natural T cells (22.76 ± 18.61%) assumed FOXP3 expression. These FOXP3-expressing CD3(+)CD56(+) cells lost the expression of IFN-γ and perforin, which are critical for the effector function of natural T cells. On the other hand, they acquired surface expression of CD25 and CTLA-4 typically found in regulatory T (Treg) cells. Consistent with the phenotypic conversion, they imposed an inhibitory effect on anti-CD3-induced proliferation of naive T cells. Further studies demonstrated that transforming growth factor β1 (TGF-β1) could effectively induce FOXP3 expression in CD3(+)CD56(+) cells and the cells were thus endowed with a potent immunosuppressive capacity. Finally, Kaplan-Meier analysis revealed that the relative abundance of FOXP3-expressing CD3(+)CD56(+) cells in tumor tissues was significantly correlated with the survival of HCC patients. In conclusion, the present study identified a new type of regulatory immune cells whose emergence in liver cancer tissues may contribute to tumor progression.
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.|Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Center of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jirun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yu
authors.affiliation: Center of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Center of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Center of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D065150:Cellular Reprogramming / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D019002:CD56 Antigen; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C522918:NCAM1 protein, human; D053773:Transforming Growth Factor beta1