Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
Immunotherapy using allogenic NK cells downregulates mitochondrial-related genes and inhibits the OXPHOS system of malignant meningioma.
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Maeoka Ryosuke, Matsuda Ryosuke, Nakazawa Tsutomu, Mochida Yuki, Ouji-Sageshima Noriko, Yamada Kengo, Morimoto Takayuki, Takeshima Yasuhiro, Yamada Shuichi, Nishimura Fumihiko, Park Young-Soo, Ito Toshihiro, Nakagawa Ichiro
Аннотация
BACKGROUND: Malignant meningiomas (MM) are highly aggressive tumors and difficult to treat. Immunotherapy might be a promising treatment for cancers, including MM. This study assessed the anti-tumor effects of highly-purified human genuine-induced natural killer cells (GiNKs) on MM.
METHODS: We evaluated the anti-tumor activity of allogeneic GiNKs with immortal human MM cell lines, IOMM-Lee and HKBMM. Inhibition of cell growth was assessed by apoptosis assay, fluorescent microscopic cytotoxic assays, and impedance-based real-time cell growth assays in vitro. We also confirmed the anti-tumor effect on MM in orthotopic xenograft murine models, and RNA sequencing analysis was performed using ex vivo MM cells from mice autopsy.
RESULTS: Allogeneic GiNKs had a positive effect on MM cells. Apoptosis assay and impedance-based real-time cell growth assays demonstrated the dose-dependent inhibitory growth effects of GiNKs on MM cell lines by inducing apoptosis (p < 0.0001 for both cell lines vs control). The intracranial administration of GiNKs prolonged the overall survival of the orthotopic xenograft MM murine models (p = 0.005 for both cell lines vs control). RNA sequencing analysis showed GiNKs downregulated mitochondrial-related genes, MT-ND1 and MT-RNR2, and inhibited the oxidative phosphorylation (OXPHOS) system of tumors derived from MM cells (p < 0.0001 for both cell lines vs control).
CONCLUSIONS: GiNKs promoted apoptosis of MM cells by downregulating mitochondrial-related genes and inhibiting the OXPHOS system. GiNKs might be a therapeutic option, in combination with other drugs such as immune checkpoint inhibitors, for patients with MM.
METHODS: We evaluated the anti-tumor activity of allogeneic GiNKs with immortal human MM cell lines, IOMM-Lee and HKBMM. Inhibition of cell growth was assessed by apoptosis assay, fluorescent microscopic cytotoxic assays, and impedance-based real-time cell growth assays in vitro. We also confirmed the anti-tumor effect on MM in orthotopic xenograft murine models, and RNA sequencing analysis was performed using ex vivo MM cells from mice autopsy.
RESULTS: Allogeneic GiNKs had a positive effect on MM cells. Apoptosis assay and impedance-based real-time cell growth assays demonstrated the dose-dependent inhibitory growth effects of GiNKs on MM cell lines by inducing apoptosis (p < 0.0001 for both cell lines vs control). The intracranial administration of GiNKs prolonged the overall survival of the orthotopic xenograft MM murine models (p = 0.005 for both cell lines vs control). RNA sequencing analysis showed GiNKs downregulated mitochondrial-related genes, MT-ND1 and MT-RNR2, and inhibited the oxidative phosphorylation (OXPHOS) system of tumors derived from MM cells (p < 0.0001 for both cell lines vs control).
CONCLUSIONS: GiNKs promoted apoptosis of MM cells by downregulating mitochondrial-related genes and inhibiting the OXPHOS system. GiNKs might be a therapeutic option, in combination with other drugs such as immune checkpoint inhibitors, for patients with MM.