title: Elevated chronic inflammatory factors and myeloid-derived suppressor cells indicate poor prognosis in advanced melanoma patients.
abstract: Chronic inflammation is considered to be one of the hallmarks for tumor initiation and progression. Moreover, a long-term production and accumulation of inflammatory factors lead to a local and systemic immunosuppression associated with cancer progression. However, the correlation between inflammatory mediators, immunosuppressive cells and the clinical outcome of malignant melanoma patients was poorly investigated. In this study, we performed a complex analysis of various inflammatory factors, myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of patients suffering from malignant melanoma of different stages. We demonstrated that levels of serum IL-1β, IFN-γ and CXCL10 were significantly increased in advanced melanoma patients. In addition, these factors were found to be associated with an increased frequency of MDSCs and Tregs as compared to age- and gender-matched healthy donors. Importantly, advanced melanoma patients with signs of progression displayed markedly elevated concentrations of IL-1β and CXCL10 as compared to patients with stable disease. Moreover, an enrichment of circulating monocytic (Mo)-MDSCs significantly correlated with a decreased progression free survival of these patients. Our data highlight a complex association between circulating inflammatory mediators, Mo-MDSCs and the clinical outcome as well as suggest that their levels in patients with advanced melanoma are of important prognostic value allowing the identification of those with high risk of disease progression.
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; Department of Obstetrics and Gynecology, Center for Reproductive Medicine, The First Hospital Affiliated to Anhui Medical University, Hefei, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Jiang
authors.forename: Christoffer
authors.initials: C
authors.lastname: Gebhardt
authors.forename: Ludmila
authors.initials: L
authors.lastname: Umansky
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.forename: Torsten J
authors.initials: TJ
authors.lastname: Schulze
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
authors.forename: Viktor
authors.initials: V
authors.lastname: Umansky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000097:blood*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C508585:IL1B protein, human; D016898:Interferon-alpha; D053583:Interleukin-1beta; D000074324:Ipilimumab
keywords: chronic inflammatory factors; immunosuppression; melanoma; myeloid-derived suppressor cells; regulatory T cells