Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties

Journal of Leukocyte Biology

Sokratis Trellakis²  Motaz Elian²  Stephan Lang²  Peter Zabel– and¹  Marcus Schenck³  Gabriele Steller⁵  Dominik Schmaltz⁵  Henrik Suttmann⁴  Jürgen Welling–¹  Sven Brandau²  Kirsten Bruderek² 

[1] –Pneumology, Research Center Borstel, Borstel, Germany;Departments of Otorhinolaryngology and Urology, University Hospital Essen, Essen, Germany;Urology, University Hospital Essen, Essen, Germany;Department of Urology, University of Lübeck, Lübeck, Germany Urology, University Hospital Essen, Essen, Germany;Departments of  Immunology and Cell Biology and Urology, University Hospital Essen, Essen, Germany;

关键词: neutrophil precursors;    head and neck cancer;    lung cancer;    bladder cancer;   

DOI  :  10.1189/jlb.0310162

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown