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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4010

Title: Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors.
Other Titles: 細胞外増幅活性Natural Killer細胞は膠芽腫由来腫瘍を移植したマウスの全生存期間を延長させる
Authors: Shida, Yoichi
Nakazawa, Tsutomu
Matsuda, Ryosuke
Morimoto, Takayuki
Nishimura, Fumihiko
Nakamura, Mitsutoshi
Maeoka, Ryosuke
Yamada, Shuichi
Nakagawa, Ichiro
Park, Young-Soo
Yasukawa, Motoaki
Tojo, Takashi
Tsujimura, Takahiro
Nakase, Hiroyuki
Keywords: PD-1
NK cell
Issue Date: 15-Sep-2021
Publisher: MDPI
Citation: International journal of molecular sciences Vol.22 No.18 Article No.9975 (2021 Sep)
Abstract: Glioblastoma (GBM) is the leading malignant intracranial tumor and is associated with a poor prognosis. Highly purified, activated natural killer (NK) cells, designated as genuine induced NK cells (GiNKs), represent a promising immunotherapy for GBM. We evaluated the anti-tumor effect of GiNKs in association with the programmed death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint pathway. We determined the level of PD-1 expression, a receptor known to down-regulate the immune response against malignancy, on GiNKs. PD-L1 expression on glioma cell lines (GBM-like cell line U87MG, and GBM cell line T98G) was also determined. To evaluate the anti-tumor activity of GiNKs in vivo, we used a xenograft model of subcutaneously implanted U87MG cells in immunocompromised NOG mice. The GiNKs expressed very low levels of PD-1. Although PD-L1 was expressed on U87MG and T98G cells, the expression levels were highly variable. Our xenograft model revealed that the retro-orbital administration of GiNKs and interleukin-2 (IL-2) prolonged the survival of NOG mice bearing subcutaneous U87MG-derived tumors. PD-1 blocking antibodies did not have an additive effect with GiNKs for prolonging survival. GiNKs may represent a promising cell-based immunotherapy for patients with GBM and are minimally affected by the PD-1/PD-L1 immune evasion axis in GBM.
Description: 博士(医学)・甲第827号・令和4年3月15日
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/10564/4010
ISSN: 14220067
DOI: https://doi.org/10.3390/ijms22189975
Academic Degrees and number: 24601A827
Degree-granting date: 2022-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2021年度

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