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Novel application of microparticles demonstrate myeloid uptake and induce phenotypic change within the brain tumor microenvironment 2254
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Researchers demonstrated that microparticles can be taken up by myeloid cells within glioblastoma tumors and can induce phenotypic changes in tumor-associated macrophages and neutrophils, suggesting that particle-based approaches may be able to modify the immunosuppressive tumor microenvironment.
Abstract Description Glioblastoma (GBM) is a common adult brain tumor with average survival of 15 - 20 months. A major barrier of immunotherapy success is an immunosuppressive tumor microenvironment (TME) induced partially by the immunosuppressive myeloid population. T cell exhaustion is driven by MHC I mediated antigen presentation by M2-like tumor associated macrophages (TAMs). Additionally, suppressive neutrophils have been found in GBM, suggesting a role in T cell suppression and/or tumor growth. Immunosuppressive myeloid cells in the TME are classified by downregulation of antigen presentation markers CD80, CD86, and MHC II. Neutrophil expression of antigen presentation markers MHC II and CD80 only occur after stimulation. Our goal is to engineer a myeloid-targeting based agent encouraging a stimulatory phenotype in suppressive myeloid cells to induce an anti-tumor response and alleviate the anti-immune phenotype of the TME. Intracranial injection of florescent microplastic beads in murine brain tumors resulted in up to 85% myeloid specific uptake, indicating targeting capacity and demonstrating increased expression of CD80 and MHC II among TAMs and neutrophils after bead injection compared to sham. In demonstrating the microparticles’ ability to drive phenotypic change, our data marks the potential for myeloid cell targeting within tumors to induce anti-tumor immune response. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
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