Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis

Morimoto, Takayuki and Nakazawa, Tsutomu and Matsuda, Ryosuke and Maeoka, Ryosuke and Nishimura, Fumihiko and Nakamura, Mitsutoshi and Yamada, Shuichi and Park, Young-Soo and Tsujimura, Takahiro and Nakagawa, Ichiro (2024) Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis. International Journal of Molecular Sciences, 25 (4). p. 2435. ISSN 1422-0067

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Abstract

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors’ ligands, inhibitory receptors’ ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.

Item Type: Article
Subjects: Universal Eprints > Multidisciplinary
Depositing User: Managing Editor
Date Deposited: 20 Feb 2024 04:28
Last Modified: 20 Feb 2024 04:28
URI: http://journal.article2publish.com/id/eprint/3633

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