IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients.
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 alpha-chain of the receptor for IL-4 (IL4Ralpha) 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, IL4Ralpha 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.
Mandruzzato
Susanna
S
Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, Padova, Italy;
Solito
Samantha
S
Falisi
Erika
E
Francescato
Samuela
S
Chiarion-Sileni
Vanna
V
Mocellin
Simone
S
Zanon
Antonio
A
Rossi
Carlo R
CR
Nitti
Donato
D
Bronte
Vincenzo
V
Zanovello
Paola
P
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D053662:Interleukin-4 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology*
C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit