Trabectedin modulates the glioma innate and adaptive immune microenvironment in vivo.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B148
Abstract ID: 5482

Presenting Author:
Matthew Nazzaro , Graduate Student at Ohio State Univ., Wexner Res. Inst., Nationwide Childrens Hosp.

Abstract:

Low-grade gliomas (LGG) are the most common brain tumor in adolescents and young adults. LGG are neglected in the field of research due to their low relative risk compared to high-grade glioblastoma despite their potential to malignantly transform into fatal high-grade gliomas (HGG). Therefore, there is a necessity to investigate and develop novel therapeutics to combat the progression of glioma. Malignant progression of glioma is associated with an accumulation of immunosuppressive myeloid cells that impair anti-tumor T cell function. Trabectedin is an FDA approved chemotherapy used in the treatment of soft tissue sarcoma. Beyond its chemotherapeutic properties, Trabectedin has been shown to selectively deplete monocytes and macrophages, but its role in the modulating the brain TME has not yet been investigated. Here, we utilized mass cytometry (CyTOF) to investigate the impact of Trabectedin on the glioma immune TME as well as the global immune system in the immunocompetent, transgenic RCAS/t-va murine glioma model which recapitulates the progression of low to high-grade glioma. Trabectedin significantly reduced bone-marrow derived myeloid cells in the glioma TME as well as splenic macrophages and monocytes. Further, Trabectedin increased the proportion of tumor-infiltrating T cells. In conclusion, Trabectedin immunomodulates the glioma TME in vivo and could potentially enhance the efficacy of immunotherapies by overcoming myeloid-driven immunosuppressive resistance.