Identification of immune evasion mechanisms in the osteosarcoma microenvironment

Division Of Basic Sciences - Nci

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Abstract

This project specifically focuses on revealing the tumor cell autonomous and non-cell autonomous mechanisms that promote immune evasion and disease progression using syngeneic murine osteosarcoma models and clinically annotated patient specimens. We have found that metastatic osteosarcoma specimens lack a robust inflammatory immune response, in part by excluding cytotoxic lymphocytes from infiltrating the pulmonary tumor mass. This investigation has also revealed various immunomodulatory cytokines and signaling pathways that are differentially expressed between primary and metastatic osteosarcoma tumors. To further investigate these data, we have recently completed a thorough evaluation and protocol optimizations for various spatial biology platforms. By combining these spatial biology technologies with single cell RNA-sequencing, we are currently engaged in an integrated multi-omic approach whereby we can resolve the molecular and cellular heterogeneity of regional microdomains within both murine and human osteosarcoma specimens.