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Journal of Translational Medicine

, 13:9

First Online: 16 January 2015Received: 22 September 2014Accepted: 26 December 2014DOI: 10.1186-s12967-014-0376-x

Cite this article as: Chevolet, I., Speeckaert, R., Schreuer, M. et al. J Transl Med 2015 13: 9. doi:10.1186-s12967-014-0376-x

Abstract

BackgroundImmune 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.

MethodsFlow 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.

ResultsCirculating 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.

ConclusionWe 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.

KeywordsMelanoma Plasmacytoid dendritic cell pDC Myeloid-derived suppressor cell MDSC Myeloid differentiation Prognosis Immunoprofiling AbbreviationsAJCCAmerican Joint Committee on Cancer system

CTLA-4Cytotoxic T Lymphocyte-Associated Antigen 4

DCDendritic cells

mDCMyeloid DC

MDSCMyeloid-derived suppressor cells

mMDSCMonocytic MDSC

OSOverall survival

PBMCPeripheral blood mononuclear cells

pDCPlasmacytoid DC

PD-L1Programmed-Death Ligand 1

PFSProgression-free survival

pmnMDSCPolymorphonuclear MDSC

TregRegulatory T-cell

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Autor: Ines Chevolet - Reinhart Speeckaert - Max Schreuer - Bart Neyns - Olga Krysko - Claus Bachert - Mireille Van Gele - Nanja 

Fuente: https://link.springer.com/







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