title: Polyphenon [corrected] E enhances the antitumor immune response in neuroblastoma by inactivating myeloid suppressor cells.
abstract: OBJECTIVE
  Neuroblastoma is a rare childhood cancer whose high risk, metastatic form has a dismal outcome in spite of aggressive therapeutic interventions. The toxicity of drug treatments is a major problem in this pediatric setting. In this study, we investigated whether Polyphenon E, a clinical grade mixture of green tea catechins under evaluation in multiple clinical cancer trials run by the National Cancer Institute (Bethesda, MD), has anticancer activity in mouse models of neuroblastoma.
  
  
  METHODS
  We used three neuroblastoma models: (i) transgenic TH-MYCN mouse developing spontaneous neuroblastomas; (ii) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenotransplanted with human SHSY5Y cells; and (iii) A/J mice transplanted with syngeneic Neuro 2A cells. Mice were randomized in control and Polyphenon E-drinking groups. Blood from patients with neuroblastoma and normal controls was used to assess the phenotype and function of myeloid cells.
  
  
  RESULTS
  Polyphenon E reduced the number of tumor-infiltrating myeloid cells, and inhibited the development of spontaneous neuroblastomas in TH-MYCN transgenic mice. In therapeutic models of neuroblastoma in A/J, but not in immunodeficient NOD/SCID mice, Polyphenon E inhibited tumor growth by acting on myeloid-derived suppressor cells (MDSC) and CD8 T cells. In vitro, Polyphenon E impaired the development and motility of MDSCs and promoted differentiation to more neutrophilic forms through the 67 kDa laminin receptor signaling and induction of granulocyte colony-stimulating factor. The proliferation of T cells infiltrating a patient metastasis was reactivated by Polyphenon E.
  
  
  CONCLUSIONS
  These findings suggest that the neuroblastoma-promoting activity of MDSCs can be manipulated pharmacologically in vivo and that green tea catechins operate, at least in part, through this mechanism.
authors: Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom.
authors: Giorgia
authors: G
authors: Santilli
authors: Izabela
authors: I
authors: Piotrowska
authors: Sandra
authors: S
authors: Cantilena
authors: Olesya
authors: O
authors: Chayka
authors: Marco
authors: M
authors: D'Alicarnasso
authors: Daniel A
authors: DA
authors: Morgenstern
authors: Nourredine
authors: N
authors: Himoudi
authors: Katie
authors: K
authors: Pearson
authors: John
authors: J
authors: Anderson
authors: Adrian J
authors: AJ
authors: Thrasher
authors: Arturo
authors: A
authors: Sala
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D017474:Receptors, Laminin / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013662:Tea / Q000737:chemistry*
chemical_list: D017474:Receptors, Laminin; D013662:Tea; D016179:Granulocyte Colony-Stimulating Factor; D002392:Catechin; C472086:polyphenon E