Contrasting Osteosarcoma and Epithelial Breast Cancer Immune Regulation in Murine Cell Lines

Document Type

Article

Publication Date

Summer 2023

Keywords

JMG

JAX Location

In: Student Reports, Summer 2023, The Jackson Laboratory

Abstract

Cancers have a complex relationship with the local immune microenvironment; in a tumor microenvironment (TME), tumor cells can reprogram immune cells to facilitate cancer growth and metastasis (Giese, et al. 2019, Lui, et al. 2021). Therefore, it is critical to understand how tumor cells functionally modulate both the innate arm (such as neutrophils) and adaptive arm (such as T cells) of the immune system in a specific TME. Improved functional understanding helps develop more effective immunotherapies by directly targeting various immunosuppressive mechanisms. In contrast to the extensive TME studies of epithelial cancers (such as breast cancer) (Gong, et al. 2022), very little is known about the roles of the TME in sarcomas. These cancers of mesenchymal origin, with fewer treatment options, have poor prognoses and a high occurrence in children (Sarcomas, soft tissue - statistics 2023). In this study, based on our previous knowledge of the immunosuppressive TME in metastatic breast cancer models (Gong, et al. 2022), we compared how a type of bone sarcoma – osteosarcoma, differs from epithelial cancer (breast cancer) in its modulation of innate and adaptive immune cells in vitro. We found a basal upregulation in inflammatory genes and reduced immunosuppression of T cells in osteosarcoma contrasted to breast cancer. These results lay a foundation for us to further characterize the underexplored TME of sarcomas in vivo.

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