Abstract 208: Transcriptional profiling of the microenvironment in pediatric osteosarcoma

Abstract

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 in 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 performed targeted gene expression profiling of metastatic and non-metastatic osteosarcoma specimens. Our profiling experiments have revealed that metastatic OS specimens are immunologically “colder” than non-metastatic OS specimens. Our data also demonstrates that T cells are largely excluded from the metastatic specimens and that this exclusion significantly correlates with markers of vascular instability. In a pathological setting, such as that of cancer, VEGF and ANG2 signaling promote vascular instability which limits leukocyte extravasation and subsequent tumor infiltration. Our data suggests that vascular destabilization mediated by VEGF/ANG2 signaling impedes T cell infiltration specifically in metastatic OS and identifies these molecules as potential targets for therapeutic intervention. Citation Format: Laurie Sorenson, Troy A. McEachron. Transcriptional profiling of the microenvironment in pediatric osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 208.