Recurrence or progression of neuroblastoma in children with MYCN amplification, 1p deletion or 11q deletion may due to altered immune status

Abstract

Background Neuroblastoma (NB) is a childhood malignancy originating from the sympathetic nervous system and is the most common extracranial malignant solid tumor in children. This study explored the prognosis of neuroblastoma patients with different genetic alterations, as well as altered peripheral blood immune status. Methods We screened 31 samples of neuroblastoma for MYCN amplification status and loss of heterozygosity at chromosome bands 1p36 and 11q23. Peripheral blood samples from these NB patients were tested for immune cells and cytokines by flow cytometry. Tests of association were performed with the use of Fisher’s exact test. Significant differences were analyzed using independent samples T-test. Survival curves were constructed according to the methods of Kaplan and Meier. Results According to FISH of pathological specimens, there were 6 patients with amplification of MYCN, 9 patients with chromosome 1p deletion, and 14 patients with chromosome 11q deletion. The event-free survival (EFS) was found to be worse in patients with MYCN amplification or 1p deletion than in the corresponding normal group by Kaplan-Meier analysis, whereas 11q deletion was a prognostic factor affecting EFS only in patients with unamplified MYCN. Changes in peripheral blood immune cells and cytokines detected by flow cytometry revealed a decrease in the proportion of tumor-infiltrating T cells (CD4 + and CD8 + T cells), an increase in regulatory T cells (Tregs), and an increase in immunosuppression-related factors interleukin (IL)-6 and IL-10. Conclusions In our analysis, NB with these genetic characteristics may have some regulatory network/signaling pathway to downregulate tumor-infiltrating T cells, upregulate suppressor cells such as Tregs, and promote the secretion of immunosuppressive cytokines IL-6 and IL-10, creating an immunosuppressive microenvironment that affects the immune response of patients and ultimately leads to a worse prognosis.