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Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors

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 as...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472834/
https://www.ncbi.nlm.nih.gov/pubmed/34576141
http://dx.doi.org/10.3390/ijms22189975
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author 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
author_facet 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
author_sort Shida, Yoichi
collection PubMed
description 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.
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spelling pubmed-84728342021-09-28 Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors 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 Int J Mol Sci Article 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. MDPI 2021-09-15 /pmc/articles/PMC8472834/ /pubmed/34576141 http://dx.doi.org/10.3390/ijms22189975 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
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
Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors
title Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors
title_full Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors
title_fullStr Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors
title_full_unstemmed Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors
title_short Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors
title_sort ex vivo expanded and activated natural killer cells prolong the overall survival of mice with glioblastoma-like cell-derived tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472834/
https://www.ncbi.nlm.nih.gov/pubmed/34576141
http://dx.doi.org/10.3390/ijms22189975
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