Low-dose aspirin delays an inflammatory tumor progression in vivo in a transgenic mouse model of neuroblastoma
Menée à l'aide d'un modèle murin, cette étude suggère que de faibles doses d'aspirine permettraient de retarder la progression tumorale associée à une inflammation chez les patients atteints d'un neuroblastome
Tumor-associated inflammation is a driving force in several adult cancers, and intake of low-dose aspirin has proven to reduce cancer incidence. Little is known about tumor-associated inflammation in pediatric neoplasms and no in vivo data exists on the effectiveness of low-dose aspirin on established tumors. The present study employs the transgenic TH-MYCN mouse model for neuroblastoma (NB) to evaluate inflammatory patterns paralleling tumor growth in vivo and low-dose aspirin as a therapeutic option for high-risk NB. Spontaneously arising abdominal tumors were monitored for tumor-associated inflammation ex-vivo at various stages of disease, and homozygous mice received daily low-dose aspirin (10mg/kg) using oral gavage or no treatment, from 4.5 to 6 weeks of age. Using flow cytometry, a transition from an adaptive immune response predominated by CD8+ T-cells in early neoplastic lesions, towards enrichment in immature cells of the innate immune system, including myeloid-derived suppressor cells, dendritic cells (DCs) and tumor-associated macrophages (TAMs), was detected during tumor progression. An M1 to M2 transition of TAMs was demonstrated, paralleled by a deterioration of DC status. Treatment with low-dose aspirin to mice homozygous for the TH-MYCN transgene significantly reduced tumor burden (p<0.01), the presence of tumor-associated cells of the innate immune system (p<0.01) as well as the intratumoral expression of TGF-β, thromboxane A2 (p<0.05) and prostaglandin D2 (p<0.01). In conclusion, tumor-associated inflammation appears as a potential therapeutic target in NB and low-dose aspirin reduces tumor burden in the TH-MYCN transgenic mouse model of NB, hence warranting further studies on aspirin in high-risk NB.
http://carcin.oxfordjournals.org/content/early/2013/01/23/carcin.bgt009.abstract