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Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma

INES CHEVOLET (UGent) , Reinhart Speeckaert (UGent) , Max Schreuer (UGent) , Bart Neyns, Olga Krysko (UGent) , Claus Bachert (UGent) , Mireille Van Gele (UGent) , Nanja van Geel (UGent) and Lieve Brochez (UGent)
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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. Conclusion: 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.
Keywords
Myeloid differentiation, Prognosis, Myeloid-derived suppressor cell (MDSC), Plasmacytoid dendritic cell (pDC), Melanoma, EXPRESSION, MODULATION, MONOCYTES, PHENOTYPE, Immunoprofiling

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MLA
CHEVOLET, INES et al. “Clinical Significance of Plasmacytoid Dendritic Cells and Myeloid-derived Suppressor Cells in Melanoma.” JOURNAL OF TRANSLATIONAL MEDICINE 13 (2015): n. pag. Print.
APA
CHEVOLET, I., Speeckaert, R., Schreuer, M., Neyns, B., Krysko, O., Bachert, C., Van Gele, M., et al. (2015). Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma. JOURNAL OF TRANSLATIONAL MEDICINE, 13.
Chicago author-date
CHEVOLET, INES, Reinhart Speeckaert, Max Schreuer, Bart Neyns, Olga Krysko, Claus Bachert, Mireille Van Gele, Nanja van Geel, and Lieve Brochez. 2015. “Clinical Significance of Plasmacytoid Dendritic Cells and Myeloid-derived Suppressor Cells in Melanoma.” Journal of Translational Medicine 13.
Chicago author-date (all authors)
CHEVOLET, INES, Reinhart Speeckaert, Max Schreuer, Bart Neyns, Olga Krysko, Claus Bachert, Mireille Van Gele, Nanja van Geel, and Lieve Brochez. 2015. “Clinical Significance of Plasmacytoid Dendritic Cells and Myeloid-derived Suppressor Cells in Melanoma.” Journal of Translational Medicine 13.
Vancouver
1.
CHEVOLET I, Speeckaert R, Schreuer M, Neyns B, Krysko O, Bachert C, et al. Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma. JOURNAL OF TRANSLATIONAL MEDICINE. 2015;13.
IEEE
[1]
I. CHEVOLET et al., “Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma,” JOURNAL OF TRANSLATIONAL MEDICINE, vol. 13, 2015.
@article{5973370,
  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.
Conclusion: 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.},
  articleno    = {9},
  author       = {CHEVOLET, INES and Speeckaert, Reinhart and Schreuer, Max and Neyns, Bart and Krysko, Olga and Bachert, Claus and Van Gele, Mireille and van Geel, Nanja and Brochez, Lieve},
  issn         = {1479-5876},
  journal      = {JOURNAL OF TRANSLATIONAL MEDICINE},
  keywords     = {Myeloid differentiation,Prognosis,Myeloid-derived suppressor cell (MDSC),Plasmacytoid dendritic cell (pDC),Melanoma,EXPRESSION,MODULATION,MONOCYTES,PHENOTYPE,Immunoprofiling},
  language     = {eng},
  pages        = {9},
  title        = {Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma},
  url          = {http://dx.doi.org/10.1186/s12967-014-0376-x},
  volume       = {13},
  year         = {2015},
}

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