Distinct signatures of the immune responses in low risk versus high risk neuroblastomaReportar como inadecuado




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Journal of Translational Medicine

, 9:170

First Online: 06 October 2011Received: 27 September 2011Accepted: 06 October 2011DOI: 10.1186-1479-5876-9-170

Cite this article as: Gowda, M., Godder, K., Kmieciak, M. et al. J Transl Med 2011 9: 170. doi:10.1186-1479-5876-9-170

Abstract

BackgroundOver 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.

MethodsWe 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.

ResultsDistinct 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.

ConclusionsThis 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.

KeywordsNeuroblastoma innate immunity adaptive immunity prognostic biomarkers Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-9-170 contains supplementary material, which is available to authorized users.

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Autor: Madhu Gowda - Kamar Godder - Maciej Kmieciak - Andrea Worschech - Maria-Libera Ascierto - Ena Wang - Francesco M Marincola

Fuente: https://link.springer.com/







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