Abstract
9565
Background: Cure rates have reached a plateau for many pediatric solid tumors. Identifying new therapeutic targets, biomarkers of response and prognostic indicators should improve clinical outcomes. Accumulation of myeloid derived suppressor cells (MDSCs) is an important mechanism of tumor mediated immune evasion. Increased levels of MDSCs in adult cancer patients correlate with a worse prognosis, and decrease in levels with treatment is associated with benefit. Little is known about MDSCs in childhood, or in children with cancer. This pilot measured levels of MDSCs in pediatric patients with cancer and healthy children. Methods: We enrolled subjects using an Institutional Review Board approved protocol after obtaining informed consent. Blood was obtained from 14 children with newly diagnosed or recurrent solid tumors at start of therapy. In 10 of these patients, levels were also drawn after therapy. Blood was obtained once from 6 healthy children in a primary care office. Samples were obtained concurrently with complete blood counts. MDSCs were measured on fresh whole blood and were defined as Lin-1+/HLADR-/CD 33+/CD11b+/ by flow. Total MDSC numbers were then calculated. Results: The mean total number of MDSCs was 596 cells/ul at diagnosis for the 14 children with cancer and 170 cells/ul for the 6 healthy children (t(18) = 3.02, p = .0073). For the 10 children with cancer who had repeat values measured after treatment, MDSCs decreased in 4 and increased in 6. The mean initial MDSC count for these children was 494 cells/ul, and the mean post treatment count was 1716 cells/ul (t(9) = 1.81, p = .1036). Larger change scores tended to be associated with children treated with alkylator therapy followed by G-CSF. The results for percent MDSC in white cells mirrored those of total number. Conclusions: Circulating MDSCs were higher in pediatric cancer patients than healthy controls. Cancer treatment did not reliably reduce MDSC levels. After some treatments, the levels increased, potentially increasing immune tolerance. Further research is needed to determine if circulating MDSCs are a reliable predictive or prognostic marker in pediatric cancer, and whether they represent a potential target for therapeutic intervention.