Increased Populations of Regulatory T Cells in Peripheral Blood of Patients with Hepatocellular Carcinoma

作者: Lars A. Ormandy , Tina Hillemann , Heiner Wedemeyer , Michael P. Manns , Tim F. Greten

DOI: 10.1158/0008-5472.CAN-04-3232

关键词: Cytokine secretionInterleukin 21ImmunologyImmunotherapyT lymphocyteIL-2 receptorAntibodyImmune systemCytotoxic T cellMedicineCancer researchOncology

摘要: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide with a poor prognosis and one for which immunotherapy remains viable option. Experimental tumor models have shown that regulatory T cells, functionally unique subset of can suppress effective antitumor immune responses. This suppression might explain outcome some protocols currently being used. A better understanding role cells in HCC important design future immunotherapy-based clinical protocols. We studied from 84 patients 74 controls, including healthy donors, chronic hepatitis B virus C infection nonviral liver cirrhosis. Regulatory were identified by fluorescence-activated cell sorting using panel antibodies real-time PCR analysis Foxp3 expression. Functional studies done to analyze their inhibitory role. Finally, analyzed tumors ascites HCC. Patients increased numbers CD4+CD25+ peripheral blood, express high levels HLA-DR, GITR, low or no CD45RA. These anergic toward T-cell receptor stimulation and, when cocultured activated CD4+CD25- potently suppressed proliferation cytokine secretion. There also tumor-infiltrating lymphocytes comparable increase blood. Our data suggest frequency play modulation response against could be immunotherapeutic approaches.

参考文章(45)
Detlef Dieckmann, Cord Henrik Bruett, Heidi Ploettner, Manfred Bernhard Lutz, Gerold Schuler, Human CD4 CD25 Regulatory, Contact-dependent T Cells Induce Interleukin 10-producing, Contact-independent Type 1-like Regulatory T Cells Journal of Experimental Medicine. ,vol. 196, pp. 247- 253 ,(2002) , 10.1084/JEM.20020642
Udaya K. Liyanage, Todd T. Moore, Hong-Gu Joo, Yoshiyuki Tanaka, Virginia Herrmann, Gerard Doherty, Jeffrey A. Drebin, Steven M. Strasberg, Timothy J. Eberlein, Peter S. Goedegebuure, David C. Linehan, Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma The Journal of Immunology. ,vol. 169, pp. 2756- 2761 ,(2002) , 10.4049/JIMMUNOL.169.5.2756
Kazuhiko Nakamura, Atsushi Kitani, Warren Strober, Cell Contact–Dependent Immunosuppression by Cd4+Cd25+Regulatory T Cells Is Mediated by Cell Surface–Bound Transforming Growth Factor β Journal of Experimental Medicine. ,vol. 194, pp. 629- 644 ,(2001) , 10.1084/JEM.194.5.629
Firouzeh Korangy, Lars A. Ormandy, Jörg S. Bleck, Jürgen Klempnauer, Ludwig Wilkens, Michael P. Manns, Tim F. Greten, Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma Clinical Cancer Research. ,vol. 10, pp. 4332- 4341 ,(2004) , 10.1158/1078-0432.CCR-04-0181
Edward Y. Woo, Heidi Yeh, Christina S. Chu, Katia Schlienger, Richard G. Carroll, James L. Riley, Larry R. Kaiser, Carl H. June, Cutting Edge: Regulatory T Cells from Lung Cancer Patients Directly Inhibit Autologous T Cell Proliferation Journal of Immunology. ,vol. 168, pp. 4272- 4276 ,(2002) , 10.4049/JIMMUNOL.168.9.4272
Lorenzo Cosmi, Francesco Liotta, Elena Lazzeri, Michela Francalanci, Roberta Angeli, Benedetta Mazzinghi, Veronica Santarlasci, Roberto Manetti, Vittorio Vanini, Paola Romagnani, Enrico Maggi, Sergio Romagnani, Francesco Annunziato, Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes Blood. ,vol. 102, pp. 4107- 4114 ,(2003) , 10.1182/BLOOD-2003-04-1320
Megan K. Levings, Romina Sangregorio, Maria-Grazia Roncarolo, Human Cd25+Cd4+ T Regulatory Cells Suppress Naive and Memory T Cell Proliferation and Can Be Expanded in Vitro without Loss of Function Journal of Experimental Medicine. ,vol. 193, pp. 1295- 1302 ,(2001) , 10.1084/JEM.193.11.1295
Michaela Dahm-Vicker, Fiona Powrie, Emma Jones, Vincenzo Cerundolo, Anna Katharina Simon, Awen Gallimore, Angharad Green, Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immunity Archive. ,vol. 2, pp. 1- 12 ,(2002)
Rumiko Kutami, Osamu Nakashima, Yoshito Wada, Masamichi Kojiro, Osamu Yamamoto, Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology ,(1998)