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

Journal of Translational Medicine

Lieve Brochez³  Nanja van Geel³  Mireille Van Gele³  Claus Bachert²  Olga Krysko²  Bart Neyns⁴  Max Schreuer¹  Reinhart Speeckaert³  Ines Chevolet³ 

[1] Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium;Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium;Department of Dermatology, Ghent University Hospital, De Pintelaan 185, Ghent, 9000, Belgium;Department of Medical Oncology, UZ-Brussel, Brussels, Belgium

关键词: Immunoprofiling;    Prognosis;    Myeloid differentiation;    Myeloid-derived suppressor cell (MDSC);    Plasmacytoid dendritic cell (pDC);    Melanoma;   

Others  :  1146390
DOI  :  10.1186/s12967-014-0376-x

 received in 2014-09-22, accepted in 2014-12-26,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Chevolet et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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