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Antitumor effects of intravenous natural killer cell infusion in an orthotopic glioblastoma xenograft murine model and gene expression profile analysis

ABSTRACT: Despite standard multimodality treatments, including maximal safe resection, te-mozolomide, radiotherapy, and tumor-treating fields, patients with glioblastoma (GBM) face dismal prognosis. Natural killer cell (NKC)-based immunotherapy appears to be a promising approach to treat GBM. We previously reported a novel technique to derive ex vivo-expanded highly activated NKCs from human peripheral blood mononuclear cells, which exhibited no-table antitumor effects against GBM cells. In this study, we performed preclinical evaluation of these NKCs in an in vivo orthotopic xenograft murine model, which was established by sub-cutaneously implanting U87MG cells in nonobese diabetes/severe combined immunodefi-ciency/IL2rγ null (NOG) mice. In this model, administering NKCs via the retro-orbital sinus prolonged the overall survival of NOG mice, indirectly indicating the growth inhibitory ef-fects of NKCs. In addition, we performed a comprehensive analysis of differentially ex-pressed genes using microarray, focusing on the expression of NKC activating receptor lig-ands, NKC inhibitory receptor ligands, chemokines, and chemokine receptors, between intra-cranial tumors treated with NKCs and non-treated intracranial tumors. We also performed differential gene expression analysis between the internal and external layers of intracranial tumors. Our findings provide crucial insights into NKC-based immunotherapy for patients with GBM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE248352 | GEO | 2023/11/27

REPOSITORIES: GEO

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