Mentor Name: Hui Feng

Neuroblastoma is the most common extracranial solid tumor in children. Furthermore, the amplification of the MYCN gene, a member of the MYC family, has contributed to approximately 50% of high-risk neuroblastoma. Research from the Feng Lab has discovered that tumor cells with high MYCN expression upregulate CKLF, a chemokine-like factor. This increase attracts CCR4-expressing CD4+ cells, helper and regulatory T cells, resulting in immunosuppression and tumor aggression. CKLF is the most expressed chemokine in various solid tumor types and is associated with predicting poor patient prognosis. Since neuroblastoma formation requires the recruitment of CD4+ cells, CLKF-CCR4 interactions play a key role in MYCN-activated tumors. Interestingly, inhibition of FOXP3, a transcription factor essential for the development and immunosuppressive function of Treg cells, in MYCN-positive zebrafish led to delayed tumor onset and progression. Furthermore, the tumors are more immunoreactive, indicated by high ifng, a cytokine, expression and higher numbers of CD8+ cells and NK cells. Therefore, we hypothesize that neuroblastoma engages in crosstalk with the immune system to enhance tumor development. Through the POST program, we will be using zebrafish as the experimental system with two primary goals. Goal 1 will be to assess how neuroblastoma impacts the thymus, specifically determining the impact of the development and function of CD4+ cells in thymus using flow cytometry. Goal 2 will be to determine the immune cell composition and function by analyzing zebrafish’s kidneys, using flow cytometry and q-RT-PCR analysis of different population of sorted cells. Zebrafish’s kidneys serve as an analogy organ to a mammal bone marrow. The objective of this study is to help determine neuroblastoma oncogenic pathways that lead to immunosuppression, this information will guide future clinical application of new immunotherapy against neuroblastoma.