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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8472834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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