title: Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation.
abstract: BACKGROUND
  Tumor 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.
  
  
  METHODS
  Maturation 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy. cristina.grange@unito.it.|Translational Center for Regenerative Medicine, Città della Salute e della Scienza, University of Turin, Torino, Italy. cristina.grange@unito.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.affiliation: Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy. marta.tapparo@gmail.com.|Translational Center for Regenerative Medicine, Città della Salute e della Scienza, University of Turin, Torino, Italy. marta.tapparo@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Tapparo
authors.affiliation: Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy. stefania.tritta@unito.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tritta
authors.affiliation: Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy. mariachiara.deregibus@unito.it.|Translational Center for Regenerative Medicine, Città della Salute e della Scienza, University of Turin, Torino, Italy. mariachiara.deregibus@unito.it.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Deregibus
authors.affiliation: Department of Surgical Sciences, Città della Salute e della Scienza, University of Turin, Torino, Italy. antonino.batt@gmail.com.
authors.forename: Antonino
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: Department of Surgical Sciences, Città della Salute e della Scienza, University of Turin, Torino, Italy. paolo.gontero@unito.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.affiliation: Department of Surgical Sciences, Città della Salute e della Scienza, University of Turin, Torino, Italy. bruno.frea@unito.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Frea
authors.affiliation: Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy. giovanni.camussi@unito.it.|Translational Center for Regenerative Medicine, Città della Salute e della Scienza, University of Turin, Torino, Italy. giovanni.camussi@unito.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000503:physiopathology; D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D000067128:Extracellular Vesicles / Q000276:immunology / Q000502:physiology*; D005260:Female; D059951:HLA-G Antigens / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D059951:HLA-G Antigens