Abstract PO-041: Multiplexed ion beam imaging to describe tumor-immune microenvironment and tumor heterogeneity in neuroblastoma

• Published in: Cancer research (Chicago, Ill.) Vol. 80; no. 21_Supplement; p. PO-041
• Main Authors: Kammersgaard, Marte B., Bosse, Marc, Martinez, Daniel, Bosse, Kristopher R., Maris, John M., Mackall, Crystal L., Angelo, Robert M., Davis, Kara L.
• Format: Journal Article
• Language: English
• Published: 01.11.2020
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.TUMHET2020-PO-041

Abstract Neuroblastoma is a tumor of the peripheral sympathetic nervous system, accounting for 10% of pediatric cancer associated deaths and the most common cancer diagnosed during infancy(1,2). This neural crest derived malignancy is characterized by clinical heterogeneity ranging from spontaneous regression in some patients to treatment resistance, metastasis and death in others(3,4). Here, we report the application of Multiplexed Ion Beam Imaging (MIBI), a single-cell, high-dimensional imaging method to determine the expression and co-expression of antigens on neuroblastoma cells and describe the local immune environment. We have optimized a 40-antibody panel to capture adrenergic or mesenchymal identity(5,6), infiltrating immune cells, tissue architecture and known neuroblastoma proteins. We optimized our antibody staining and determined tissue specificity using a unique tissue microarray which included 32 NBL cores but also additional childhood solid tumors including osteosarcoma, glioblastoma, Ewing’s sarcoma, rhabdomyosarcoma, atypical teratoid rhabdoid tumor, and Wilms tumor. Healthy pediatric tissues from various organs including kidney, liver, and tonsil were also included. We have uncovered divergent neuroblastoma cell populations differentiated by co-expression of CD57, Ki67 and GPC2 as well as mesenchymal (FN1 and SNAI2/SLUG) and adrenergic (TH, GATA3 and PHOX2B) antibodies, demonstrating promising early results of our application of MIBI. We will describe infiltrating immune populations and spatial relationships to these unique tumor cell populations. Our work demonstrates the feasibility of using MIBI to make translatable discoveries in neuroblastoma and other childhood cancers. With this we will lay the foundation for future discovery and validation of novel targets for immunotherapy in neuroblastoma. Citation Format: Marte B. Kammersgaard, Marc Bosse, Daniel Martinez, Kristopher R. Bosse, John M. Maris, Crystal L. Mackall, Robert M. Angelo, Kara L. Davis. Multiplexed ion beam imaging to describe tumor-immune microenvironment and tumor heterogeneity in neuroblastoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-041.