Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation

BMC Cancer

Research Article

Stefania Tritta¹  Marta Tapparo²  Giovanni Camussi²  Maria Chiara Deregibus²  Cristina Grange²  Paolo Gontero³  Bruno Frea³  Antonino Battaglia³ 

[1] Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy;Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy;Translational Center for Regenerative Medicine, Città della Salute e della Scienza, University of Turin, Torino, Italy;Department of Surgical Sciences, Città della Salute e della Scienza, University of Turin, Torino, Italy;

关键词: Extracellular vesicles;    Exosomes;    Microvesicles;    Renal cancer stem cells;    Immune-escape;   

DOI  :  10.1186/s12885-015-2025-z

 received in 2015-07-02, accepted in 2015-12-16,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundTumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105+ CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105- TCs) and their EVs.MethodsMaturation of monocyte-derived DCs was studied in presence of CD105+ CSCs and CD105- TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors.ResultsThe results obtained demonstrate that both CD105+ CSCs and CD105- TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105+ CSCs was significantly greater than that of CD105- TCs. EVs derived from CD105+ CSCs and in less extent, those derived from CD105- TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation.ConclusionsIn conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.

【 授权许可】

CC BY   
© Grange et al. 2015