title: Distinct signatures of the immune responses in low risk versus high risk neuroblastoma.
abstract: BACKGROUND
  Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.
  
  
  METHODS
  We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1β, a cytokines which is involved in the innate immune responses.
  
  
  RESULTS
  Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC) compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1β induced expression of cytokines of the innate immune responses.
  
  
  CONCLUSIONS
  This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients.
authors: Department of Pediatrics, Children's Hospital of Richmond, Richmond, VA, USA. MSGowda@mcvh-vcu.edu
authors: Madhu
authors: M
authors: Gowda
authors: Kamar
authors: K
authors: Godder
authors: Maciej
authors: M
authors: Kmieciak
authors: Andrea
authors: A
authors: Worschech
authors: Maria-Libera
authors: ML
authors: Ascierto
authors: Ena
authors: E
authors: Wang
authors: Francesco M
authors: FM
authors: Marincola
authors: Masoud H
authors: MH
authors: Manjili
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D022423:Myeloid Cells / Q000276:immunology; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D012307:Risk Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators