title: A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma.
abstract: Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR(-/low), CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI) < 12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI.
authors.affiliation: Department of Clinical and Experimental Immunology, Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia ivanivanstanojevic@gmail.com.
authors.forename: Ivan
authors.initials: I
authors.lastname: Stanojevic
authors.affiliation: Department of Histopathology, Dorset County Hospital NHS Foundation Trust, DT1 2JY Dorchester, UK.
authors.forename: Karolina
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Dermatovenerology, Military Medical Academy, 11000 Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Kandolf-Sekulovic
authors.affiliation: Department of Dermatovenerology, Military Medical Academy, 11000 Belgrade, Serbia.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Mijuskovic
authors.affiliation: Institute for Pathology, Military Medical Academy, 11000 Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Zolotarevski
authors.affiliation: Institute for Pathology, Military Medical Academy, 11000 Belgrade, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Jovic
authors.affiliation: Clinic for Plastic and Reconstructive Surgery, Military Medical Academy, 11000 Belgrade, Serbia.
authors.forename: Milomir
authors.initials: M
authors.lastname: Gacevic
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Djukic
authors.affiliation: Clinical Center of Kragujevac, 34000 Kragujevac, Serbia.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Arsenijevic
authors.affiliation: Department of Clinical and Experimental Immunology, Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
authors.forename: Danilo
authors.initials: D
authors.lastname: Vojvodic
mesh_terms: D063646:Carcinogenesis / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D022423:Myeloid Cells / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*
keywords: MDSC; immunophenotype; progression; subset