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IL4Rα+ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients

2009; American Association of Immunologists; Volume: 182; Issue: 10 Linguagem: Inglês

10.4049/jimmunol.0803831

1550-6606

Susanna Mandruzzato, Samantha Solito, Erika Falisi, Samuela Francescato, Vanna Chiarion‐Sileni, Simone Mocellin, Antonio Zanon, Carlo Riccardo Rossi, Donato Nitti, Vincenzo Bronte, Paola Zanovello,

Immune Response and Inflammation

Abstract 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 α-chain of the receptor for IL-4 (IL4Rα) 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, IL4Rα 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.