Surfaceome profiling of rhabdomyosarcoma reveals b7-h3 as a mediator of immune evasion

Roxane R. Lavoie, Patricio C. Gargollo, Mohamed E. Ahmed, Yohan Kim, Emily Baer, Doris A. Phelps, Cristine M. Charlesworth, Benjamin J. Madden, Liguo Wang, Peter J. Houghton, John Cheville, Haidong Dong, Candace F. Granberg, Fabrice Lucien

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number4528
JournalCancers
Volume13
Issue number18
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • B7-H3
  • Cell surface proteomics
  • Rhabdomyosarcoma
  • Targeted therapies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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