NK cell activity in the tumor microenvironment

The formation of an immunosuppressive tumor microenvironment (TME) impairs natural killer (NK) cell infiltration and persistence within tumor tissue and significantly diminishes NK-mediated cytotoxicity. This presents a substantial barrier to the efficacy of NK cell therapy in solid tumors. Current...

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Main Authors: A. V. Kuznetsova, X. A. Glukhova, I. P. Beletsky, A. A. Ivanov
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1609479/full
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author A. V. Kuznetsova
A. V. Kuznetsova
X. A. Glukhova
I. P. Beletsky
A. A. Ivanov
author_facet A. V. Kuznetsova
A. V. Kuznetsova
X. A. Glukhova
I. P. Beletsky
A. A. Ivanov
author_sort A. V. Kuznetsova
collection DOAJ
description The formation of an immunosuppressive tumor microenvironment (TME) impairs natural killer (NK) cell infiltration and persistence within tumor tissue and significantly diminishes NK-mediated cytotoxicity. This presents a substantial barrier to the efficacy of NK cell therapy in solid tumors. Current strategies aim to overcome immune evasion by enhancing NK cell recognition and cytotoxicity, while promoting their persistence, infiltration, and resistance to the TME. This review focusses on the biophysical characteristics of TME and specific components of the extracellular matrix (ECM) that affect NK cell activity, with the goal of identifying therapeutic approaches to modulate the TME and create a supportive niche for adaptive immune cell function. Advancements in interdisciplinary collaborations integrating oncology, cell biology, physics, engineering, materials science, and nanotechnology are crucial in advancing therapeutic strategies targeting ECM rigidity and mechanotransduction signaling pathways.
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publisher Frontiers Media S.A.
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spelling doaj-art-45af75bd2cf64d1da2a5df8e20b5adde2025-08-20T02:17:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-05-011310.3389/fcell.2025.16094791609479NK cell activity in the tumor microenvironmentA. V. Kuznetsova0A. V. Kuznetsova1X. A. Glukhova2I. P. Beletsky3A. A. Ivanov4Laboratory of Molecular and Cellular Pathology, Russian University of Medicine, Ministry of Health of the Russian Federation, Moscow, RussiaLaboratory of Regenerative Biology, Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, RussiaOnni Biotechnologies Ltd., Helsinki, FinlandOnni Biotechnologies Ltd., Helsinki, FinlandLaboratory of Molecular and Cellular Pathology, Russian University of Medicine, Ministry of Health of the Russian Federation, Moscow, RussiaThe formation of an immunosuppressive tumor microenvironment (TME) impairs natural killer (NK) cell infiltration and persistence within tumor tissue and significantly diminishes NK-mediated cytotoxicity. This presents a substantial barrier to the efficacy of NK cell therapy in solid tumors. Current strategies aim to overcome immune evasion by enhancing NK cell recognition and cytotoxicity, while promoting their persistence, infiltration, and resistance to the TME. This review focusses on the biophysical characteristics of TME and specific components of the extracellular matrix (ECM) that affect NK cell activity, with the goal of identifying therapeutic approaches to modulate the TME and create a supportive niche for adaptive immune cell function. Advancements in interdisciplinary collaborations integrating oncology, cell biology, physics, engineering, materials science, and nanotechnology are crucial in advancing therapeutic strategies targeting ECM rigidity and mechanotransduction signaling pathways.https://www.frontiersin.org/articles/10.3389/fcell.2025.1609479/fullhuman natural killer cellstumor microenvironmentextracellular matrixnew targetsanti-NK cell signaling
spellingShingle A. V. Kuznetsova
A. V. Kuznetsova
X. A. Glukhova
I. P. Beletsky
A. A. Ivanov
NK cell activity in the tumor microenvironment
Frontiers in Cell and Developmental Biology
human natural killer cells
tumor microenvironment
extracellular matrix
new targets
anti-NK cell signaling
title NK cell activity in the tumor microenvironment
title_full NK cell activity in the tumor microenvironment
title_fullStr NK cell activity in the tumor microenvironment
title_full_unstemmed NK cell activity in the tumor microenvironment
title_short NK cell activity in the tumor microenvironment
title_sort nk cell activity in the tumor microenvironment
topic human natural killer cells
tumor microenvironment
extracellular matrix
new targets
anti-NK cell signaling
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1609479/full
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AT aaivanov nkcellactivityinthetumormicroenvironment