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

Chevolet I1, Speeckaert R2, Schreuer M3,4, Neyns B5, Krysko O6, Bachert C7, Van Gele M8, van Geel N9, Brochez L10.

J Transl Med. 2015 Jan 16;13(1):9.

Show Affiliations

1Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. [email protected]

2Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. [email protected]

3Department of Medical Oncology, UZ-Brussel, Brussels, Belgium. [email protected]

4Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium. [email protected]

5Department of Medical Oncology, UZ-Brussel, Brussels, Belgium. [email protected]

6Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium. [email protected]

7Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium. [email protected]

8Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. [email protected]

9Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. [email protected]

10Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. [email protected] 

 

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 dendritic cells  (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  plasmacytoid dendritic cells levels were decreased in patients with advanced (P = 0.001) or active (P = 0.002) disease. Low  plasmacytoid dendritic cells levels conferred an independent negative impact on overall (P = 0.025) and progression-free survival (P = 0.036). Even before relapse, a decrease in  plasmacytoid dendritic cells 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).  Plasmacytoid dendritic cells and MDSCs were inversely correlated (P = 0.004). The impact of  plasmacytoid dendritic cells 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 inmelanoma 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.

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Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma.- - Global Medical Discovery