AI Article Synopsis

  • Novel therapeutic approaches are required for rhabdomyosarcoma (RMS), a common soft-tissue cancer in children, highlighting the need for new treatment options.
  • Researchers identified B7-H3 as a key regulatory protein predominantly found in RMS tumors, absent in normal tissues, making it a potential treatment target.
  • The study suggests that targeting B7-H3 might enhance T-cell responses against RMS tumors, offering insights for developing innovative immunotherapies.

Article Abstract

Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins enriched in RMS tumors. Among the top candidates, we identified B7-H3 as the major immunoregulatory molecule expressed by RMS tumors. By using a large cohort of tissue specimens, we demonstrated that B7-H3 is expressed in a majority of RMS tumors while not detected in normal human tissues. Through a deconvolution analysis of the RMS tumor RNA-seq data, we showed that B7-H3-rich tumors are enriched in macrophages M1, NK cells, and depleted in CD8-T cells. Furthermore, in vitro functional assays showed that B7-H3 knockout in RMS tumor cells increases T-cell mediated cytotoxicity. Altogether, our study uncovers new potential targets for the treatment of RMS and provides the first biological insights into the role of B7-H3 in RMS biology, paving the way for the development of next-generation immunotherapies.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466404PMC
http://dx.doi.org/10.3390/cancers13184528DOI Listing

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