title: Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma.
abstract: BACKGROUND
  Immune markers in the peripheral blood of melanoma patients could provide prognostic information. However, there is currently no consensus on which circulating cell types have more clinical impact. We therefore evaluated myeloid-derived suppressor cells (MDSC), dendritic cells (DC), cytotoxic T-cells and regulatory T-cells (Treg) in a series of blood samples of melanoma patients in different stages of disease.
  
  
  METHODS
  Flow cytometry was performed on peripheral blood mononuclear cells of 69 stage I to IV melanoma patients with a median follow-up of 39 months after diagnosis to measure the percentage of monocytic MDSCs (mMDSCs), polymorphonuclear MDSCs (pmnMDSCs), myeloid DCs (mDCs), plasmacytoid DCs (pDCs), cytotoxic T-cells and Tregs. We also assessed the expression of PD-L1 and CTLA-4 in cytotoxic T-cells and Tregs respectively. The impact of cell frequencies on prognosis was tested with multivariate Cox regression modelling.
  
  
  RESULTS
  Circulating pDC levels were decreased in patients with advanced (P = 0.001) or active (P = 0.002) disease. Low pDC levels conferred an independent negative impact on overall (P = 0.025) and progression-free survival (P = 0.036). Even before relapse, a decrease in pDC levels was observed (P = 0.002, correlation coefficient 0.898). High levels of circulating MDSCs (>4.13%) have an independent negative prognostic impact on OS (P = 0.012). MDSC levels were associated with decreased CD3+ (P < 0.001) and CD3 + CD8+ (P = 0.017) T-cell levels. Conversely, patients with high MDSC levels had more PD-L1+ T-cells (P = 0.033) and more CTLA-4 expression by Tregs (P = 0.003). pDCs and MDSCs were inversely correlated (P = 0.004). The impact of pDC levels on prognosis and prediction of the presence of systemic disease was stronger than that of MDSC levels.
  
  
  CONCLUSIONS
  We demonstrated that circulating pDC and MDSC levels are inversely correlated but have an independent prognostic value in melanoma patients. These cell types represent a single immunologic system and should be evaluated together. Both are key players in the immunological climate in melanoma patients, as they are correlated with circulating cytotoxic and regulatory T-cells. Circulating pDC and MDSC levels should be considered in future immunoprofiling efforts as they could impact disease management.
authors.affiliation: Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. ines.chevolet@ugent.be.
authors.forename: Ines
authors.initials: I
authors.lastname: Chevolet
authors.affiliation: Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. reinhart.speeckaert@ugent.be.
authors.forename: Reinhart
authors.initials: R
authors.lastname: Speeckaert
authors.affiliation: Department of Medical Oncology, UZ-Brussel, Brussels, Belgium. max.schreuer@uzbrussel.be.|Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium. max.schreuer@uzbrussel.be.
authors.forename: Max
authors.initials: M
authors.lastname: Schreuer
authors.affiliation: Department of Medical Oncology, UZ-Brussel, Brussels, Belgium. bart.neyns@uzbrussel.be.
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
authors.affiliation: Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium. olga.krysko@ugent.be.
authors.forename: Olga
authors.initials: O
authors.lastname: Krysko
authors.affiliation: Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium. Claus.Bachert@UGent.be.
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
authors.affiliation: Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. mireille.vangele@ugent.be.
authors.forename: Mireille
authors.initials: M
authors.lastname: Van Gele
authors.affiliation: Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. nanja.vangeel@ugent.be.
authors.forename: Nanja
authors.initials: N
authors.lastname: van Geel
authors.affiliation: Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. lieve.brochez@UGent.be.
authors.forename: Lieve
authors.initials: L
authors.lastname: Brochez
mesh_terms: D000328:Adult; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D018572:Disease-Free Survival; D006801:Humans; D016015:Logistic Models; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma