Natural killer cells: the immune frontline against circulating tumor cells

Abstract Natural killer (NK) play a key role in controlling tumor dissemination by mediating cytotoxicity towards cancer cells without the need of education. These cells are pivotal in eliminating circulating tumor cells (CTCs) from the bloodstream, thus limiting cancer spread and metastasis. Howeve...

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Main Authors: Doryan Masmoudi, Martin Villalba, Catherine Alix-Panabières
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Experimental & Clinical Cancer Research
Subjects:
Online Access:https://doi.org/10.1186/s13046-025-03375-x
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author Doryan Masmoudi
Martin Villalba
Catherine Alix-Panabières
author_facet Doryan Masmoudi
Martin Villalba
Catherine Alix-Panabières
author_sort Doryan Masmoudi
collection DOAJ
description Abstract Natural killer (NK) play a key role in controlling tumor dissemination by mediating cytotoxicity towards cancer cells without the need of education. These cells are pivotal in eliminating circulating tumor cells (CTCs) from the bloodstream, thus limiting cancer spread and metastasis. However, aggressive CTCs can evade NK cell surveillance, facilitating tumor growth at distant sites. In this review, we first discuss the biology of NK cells, focusing on their functions within the tumor microenvironment (TME), the lymphatic system, and circulation. We then examine the immune evasion mechanisms employed by cancer cells to inhibit NK cell activity, including the upregulation of inhibitory receptors. Finally, we explore the clinical implications of monitoring circulating biomarkers, such as NK cells and CTCs, for therapeutic decision-making and emphasize the need to enhance NK cell-based therapies by overcoming immune escape mechanisms.
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issn 1756-9966
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publishDate 2025-04-01
publisher BMC
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series Journal of Experimental & Clinical Cancer Research
spelling doaj-art-79a2f704cd564e2a93d75ede1fd83e2c2025-08-20T03:06:58ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-04-0144111510.1186/s13046-025-03375-xNatural killer cells: the immune frontline against circulating tumor cellsDoryan Masmoudi0Martin Villalba1Catherine Alix-Panabières2Laboratory of Rare Circulating Human Cells, University Medical Center of MontpellierIRMB, Univ Montpellier, INSERM, CHU Montpellier, CNRSLaboratory of Rare Circulating Human Cells, University Medical Center of MontpellierAbstract Natural killer (NK) play a key role in controlling tumor dissemination by mediating cytotoxicity towards cancer cells without the need of education. These cells are pivotal in eliminating circulating tumor cells (CTCs) from the bloodstream, thus limiting cancer spread and metastasis. However, aggressive CTCs can evade NK cell surveillance, facilitating tumor growth at distant sites. In this review, we first discuss the biology of NK cells, focusing on their functions within the tumor microenvironment (TME), the lymphatic system, and circulation. We then examine the immune evasion mechanisms employed by cancer cells to inhibit NK cell activity, including the upregulation of inhibitory receptors. Finally, we explore the clinical implications of monitoring circulating biomarkers, such as NK cells and CTCs, for therapeutic decision-making and emphasize the need to enhance NK cell-based therapies by overcoming immune escape mechanisms.https://doi.org/10.1186/s13046-025-03375-xCancerLiquid BiopsyCirculating tumor cellsNatural killer cellsBiomarkers
spellingShingle Doryan Masmoudi
Martin Villalba
Catherine Alix-Panabières
Natural killer cells: the immune frontline against circulating tumor cells
Journal of Experimental & Clinical Cancer Research
Cancer
Liquid Biopsy
Circulating tumor cells
Natural killer cells
Biomarkers
title Natural killer cells: the immune frontline against circulating tumor cells
title_full Natural killer cells: the immune frontline against circulating tumor cells
title_fullStr Natural killer cells: the immune frontline against circulating tumor cells
title_full_unstemmed Natural killer cells: the immune frontline against circulating tumor cells
title_short Natural killer cells: the immune frontline against circulating tumor cells
title_sort natural killer cells the immune frontline against circulating tumor cells
topic Cancer
Liquid Biopsy
Circulating tumor cells
Natural killer cells
Biomarkers
url https://doi.org/10.1186/s13046-025-03375-x
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