Myeloid-derived-supressor cells as regulators of th eimmune system

C.L. Jones, Gintaras Sudzius, Diana Mieliauskaite, Almantas Siaurys, Rita Viliene, Irena Butrimiene, Dainius Characiejus, Irena Dumalakiene, Vernon C. Maino, Holden T. Maecker, Dong Wang, Guangyu An, Shengzhi Xie, Yajuan Yao, Guosheng Feng, E C Wang, P J Lehner, Deborah S Cunninghame Graham, L K Borysiewicz, Justin LewisTammy Speers, Pilar Brito-Zerón, Hoda Gheitasi, Soledad Retamozo, Albert Bové, María C. Londoño, Jose-Maria Sánchez-Tapias, Miguel Caballero, Belchin Kostov, Xavier Forns, Srini V Kaveri, Manuel Ramos-Casals, Yazan S. Khaled, Basil J. Ammori, Eyad Elkord, Diana Mieliauskaite, Irena Dumalakiene, Gintaras Sudzius, Ieva Narkeviciute, Bianca Rovati, S Mariucci, M Manzoni, K Bencardino, M Danova, Susanna Hausmann-muela, Joan Muela Ribera, Elizabeth Toomer, Koen Peeters Grietens, Claudia A. Dumitru, Katrin Moses, Sokratis Trellakis, Stephan Lang, Sven Brandau, Frédéric Coutant, Pierre Miossec, Anum Fayyaz, Biji T. Kurien, R. Hal Scofield, G. HERNANDEZ-MOLINA, C. AVILA-CASADO, F. CARDENAS-VELAZQUEZ, Carlos Andres Hernandez Garcia, M. L. CALDERILLO, V. MARROQUIN, V. SOTO-ABRAHAM, C. RECILLAS-GISPERT, J. SANCHEZ-GUERRERO, Shaye Kivity, Maria Teresa Arango, Michael Ehrenfeld, Omer Tehori, Yehuda Shoenfeld, Juan Manuel Anaya, Nancy Agmon-Levin, K E Aziz, P J McCluskey, D Wakefield, Gintaras Sudzius, Diana Mieliauskaite, Almantas Siaurys, Rita Viliene, Irena Butrimiene, Dainius Characiejus, Irena Dumalakiene, Davide Lucchesi, Costantino Pitzalis, Michele Bombardieri, Arnaud Dupuy D'Angeac, Serge Monier, Darrell Pilling, Adolfo Travaglio-Encinoza, Thierry Rème, Mike Salmon, Dörte Hamann, Marijke Th.L Roos, René a.W van Lier, Daniele Focosi, Marco Bestagno, Oscar Burrone, Mario Petrini, Ryo Okada, Takaaki Kondo, Fumichika Matsuki, Hiroshi Takata, Masafumi Takiguchi, Jill M Kramer, Samantha Solito, Ilaria Marigo, Laura Pinton, Vera Damuzzo, Susanna Mandruzzato, Vincenzo Bronte, Tim F Greten, Michael P Manns, Firouzeh Korangy, Author Manuscript, Byung Ha Lee, Adrienne E. Gauna, Kaleb M. Pauley, Yun-Jong Park, Seunghee Cha

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211 Scopus citations

Abstract

In tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.
Original languageEnglish (US)
Pages (from-to)162-174
Number of pages12
JournalNature Reviews Immunology
Volume9
DOIs
StatePublished - Mar 1 2009

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