Abstract A213: Exploit the zebrafish to study lymphocyte infiltration in MYCN-amplified neuroblastoma

Abstract

Abstract Neuroblastoma is one of the most common pediatric solid tumors that derives from sympathetic nerve ganglia. Children with MYCN-amplified tumors have a very poor prognosis. MYCN amplification is associated with impaired inflammatory profiles and reduced numbers of tumor-infiltrating cytotoxic T-lymphocytes (CTL). However, it remains elusive how MYCN blocks the trafficking of T-cells to tumors and protects tumor cells escaping from CTL-mediated cytotoxicity. Elucidation of the mechanism by which MYCN suppresses immune surveillance in the neuroblastoma microenvironment could lead to improved treatment outcomes through immunotherapy. We generated a zebrafish model, in which lymphocytes and tumor cells were differentially labeled with red and green fluorochromes. We monitored these fish for trafficking of mCherry-labeled lymphocytes to EGFP-positive MYCN-overexpressing premalignant neural crests on 5, 14, and 21 days post fertilization (dpf). We found that MYCN-overexpressing premalignant neural crests could attract lymphocytes in living fish. To observe lymphocyte infiltration in different stages of tumor development, we will perform cryosection and quantify lymphocyte infiltration in each stage of tumor development. While this zebrafish model is useful in studying the behaviors of immune cells at different stages of tumor development, it can be further exploited to understand how MYCN regulates immune escape and how immune cell infiltration can be enhanced in MYCN-amplified neuroblastoma to suppress tumor onset and progression. This knowledge is critical for development of more efficient immunotherapies in treating children with neuroblastoma. Citation Format: Xiaodan Qin, Andrew Lam, Hui Feng. Exploit the zebrafish to study lymphocyte infiltration in MYCN-amplified neuroblastoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A213.