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

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. In this study, we performed preclinical evaluation of these NKCs in an in vivo orthotopic xenograft murine model, which was established by subcutaneously implanting U87MG cells in nonobese diabetes/severe combined immunodeficiency/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 effects of NKCs. In addition, we performed a comprehensive analysis of differentially expressed genes using microarray, focusing on the expression of NKC activating receptor ligands, NKC inhibitory receptor ligands, chemokines, and chemokine receptors, between intracranial tumors treated with NKCs and non-treated intracranial tumors. We also performed differential gene expression analysis between the in-ternal and external layers of intracranial tumors.