TY  - JOUR
A1  - Gowda, Madhu
A1  - Godder, Kamar
A1  - Kmieciak, Maciej
A1  - Worschech, Andrea
A1  - Ascierto, Maria-Libera
A1  - Wang, Ena
A1  - Francesco M., Marincola
A1  - Manjili, Masoud H.
T1  - Distinct signatures of the immune responses in low risk versus high risk neuroblastoma
JF  - Journal of Translational Medicine
N2  - 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-1 beta, 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-1b 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.
KW  - Neural precursor cells
KW  - Retinoic acid
KW  - Ifn-gamma
KW  - Progenitor cells
KW  - Breast-cancer
KW  - T-lymphocytes
KW  - IN-VIVO
KW  - Differentiation
KW  - Pathway
KW  - Activation
KW  - Neuroblastoma
KW  - innate immunity
KW  - adaptive immunity
KW  - prognostic biomarkers
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135147
VL  - 9
IS  - 170
ER  -