OCT 10, 2019 10:30 AM PDT

Transcriptional Profiling of the Pediatric Tumor Microenvironment

Sponsored by: NanoString Technologies
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Assistant Professor of Research, Translational Genomics, University of Southern California, Keck School of Medicine
    Biography
      Dr. McEachron received his PhD in Cellular and Molecular Pathology from the University of North Carolina at Chapel Hill and completed postdoctoral training at both the St. Jude Children's Research Hospital and at the Translational Genomics Research Institute. Dr. McEachron is currently an Assistant Professor in the Department of Translational Genomics and the Department of Pediatrics at the Keck School of Medicine of the University of Southern California. Dr. McEachron's research employs integrated multi-parametric approaches to reveal how the genomic complexity of pediatric osteosarcoma influences the tumor microenvironment and, in response, how the microenvironment supports the growth of such genomically unstable tumors. Dr. McEachron's research interests reflect his diverse training history which includes the molecular dissection of autocrine and paracrine signaling mechanisms between tumor and host using in vitro and in vivo models, the characterization of genetically engineered mouse models of pediatric brain tumors, and the interpretation and functional validation next generation sequencing data from recurrent/refractory pediatric cancer patients for clinical decision making.

    Abstract

    Osteosarcoma (OS) is the most common bone tumor in pediatric and adolescent/young adult patients. Over the past three decades, significant improvements in the survival rates or therapeutic approaches for these patients have not been made, especially in the context of metastatic disease. While immune checkpoint blockade has revolutionized the therapeutic landscape of various adult malignancies, its impact in OS has been largely underwhelming. Currently, it is unknown whether the lack of therapeutic benefit of immune checkpoint inhibition observed in patients with OS is truly due to treatment inefficacy rather than a limited understanding of the tumor microenvironment that supports this aggressive disease. To address this knowledge gap, we have profiled metastatic and non-metastatic osteosarcoma specimens using NanoString’s PanCancerIO360™ Gene Expression Panel. Our results show that metastatic specimens exhibit lymphocyte exclusion and immunohistochemistry confirms that T cells are confined to the periphery of the pulmonary lesions. Our data also provides evidence of vascular dysfunction in metastatic OS indicated by increased expression of VEGFA, an increased ANGPT2:ANGPT1 gene expression ratio, and decreased expression of SELE. Correlation analyses show an inverse relationship between lymphocyte abundance and markers of vascular dysfunction exclusively in the metastatic specimens. Together, our data shows that the non-metastatic OS specimens expressed increased levels of various immunotherapeutic targets in comparison metastatic specimens and identifies vascular dysfunction and lymphocyte exclusion as important processes for therapeutic intervention in metastatic disease.

    FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.

    Learning Objectives: 

    1. Understand the complexity behind the response of osteosarcoma to immunotherapy
    2. Learn the difference between the immune infiltrate of metastatic and non-metastatic osteosarcoma


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