Identification of immune evasion mechanisms in the osteosarcoma microenvironment

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Our current research aims to further investigate the processes associated with immune evasion of metastatic osteosarcoma and to identify therapeutic vulnerabilities for clinical translation. The first step to accomplishing this objective is to perform a thorough characterization of metastatic osteosarcoma specimens obtained from pediatric patients. We have established a workflow to enable multi-omic profiling of archived patient specimens using both formalin fixed paraffin embedded and frozen tissues. To date, we have performed spatial transcriptional profiling, imaging mass cytometry, single nuclei sequencing, cytokine profiling, and phospho-proteomics on a cohort of patient specimens. We are currently analyzing the data generated from each of these platforms. Thus far, analysis of the spatial profiling data has elucidated the transcriptional architecture of metastatic osteosarcoma. Additionally, our analysis has revealed that multiple spatially-defined molecular and cellular immunosuppressive mechanisms exist in pulmonary metastatic osteosarcoma. We have identified several immunoregulatory biological processes, cellular subsets, and cytokine pathways and are in the process of functionally validating the targets to evaluate their therapeutic potential in this disease context. The imaging mass cytometry data has been used to provide deep single cell immunophenotyping of metastatic osteosarcoma specimens, leading to a detailed spatially-resolved immunotherapeutic landscape of this disease. The single nuclei sequencing, cytokine profiling, and phospho-proteomic data are in early stages of analysis. We anticipate that, upon completing all analyses, we will have defined the transcriptional and proteomic landscape of metastatic osteosarcoma and will have credentialed therapeutic targets using both functional in vitro and in vivo studies.