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IL4R⁺ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients¹

Susanna Mandruzzato^*,, Samantha Solito^*, Erika Falisi^*, Samuela Francescato^2,*, Vanna Chiarion-Sileni, Simone Mocellin, Antonio Zanon, Carlo R. Rossi, Donato Nitti, Vincenzo Bronte^3, and Paola Zanovello^*,

^* Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, Padova, Italy; Istituto di Ricerca e Cura a Carattere Scientifico, Istituto Oncologico Veneto (IRRCS-IOV), Padova, Italy; and Department of Oncology and Surgical Sciences, Surgery Section, University of Padova, Padova, Italy

Myeloid-derived suppressor cells (MDSC) contribute to immune dysfunctions induced by tumors both in experimental models and patients. In mice, MDSC are phenotypically heterogeneous cells that vary in their surface markers, likely depending on soluble factors produced by different tumors. We recently described a subset of inflammatory monocytes with immunosuppressive properties that can be found within the tumor mass, blood, and lymphoid organs of tumor-bearing mice. These cells expressed the -chain of the receptor for IL-4 (IL4R) that was critical for their negative activity on CD8⁺ T cells. In cancer patients, the nature of MDSC is still poorly defined because evidence exists for both monocytic and granulocytic features. We show in this study that myeloid cells with immunosuppressive properties accumulate both in mononuclear and polymorphonuclear fractions of circulating blood leukocytes of patients with colon cancer and melanoma, thus unveiling a generalized alteration in the homeostasis of the myeloid compartment. Similarly to mouse MDSC, IL4R is up-regulated in both myeloid populations but its presence correlates with an immunosuppressive phenotype only when mononuclear cells, but not granulocytes, of tumor-bearing patients are considered.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC), project RSF/2005/R/5 from Fondazione Italiana Sclerosi Multipla (FISM), Progetto di Ricerca di Ateneo 2006, and Azione Biotech, Regione Veneto.

² Current address: Department of Pediatrics, University of Padova, Padova, Italy

³ Address correspondence and reprint requests to Dr. Vincenzo Bronte, Istituto di Ricerca e Cura a Carattere Scientifico, Istituto Oncologico Veneto (IRRCS-IOV), Via Gattamelata, Padova, Italy. E-mail address: enzo.bronte{at}unipd.it

⁴ Abbreviations used in this paper: TAA, tumor-associated Ag; MDSC, myeloid-derived suppressor cell; ARG, arginase; PMN, polymorphonuclear cell; IL4R, -chain of the receptor IL-4.