Senescence, NK cells, and cancer: navigating the crossroads of aging and disease

Cellular senescence, a state of stable cell cycle arrest, acts as a double-edged sword in cancer biology. In young organisms, it acts as a barrier against tumorigenesis, but in the aging population, it may facilitate tumor growth and metastasis through the senescence-associated secretory phenotype (...

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Main Authors: Marina Gergues, Rafijul Bari, Sharmila Koppisetti, Anna Gosiewska, Lin Kang, Robert J. Hariri
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565278/full
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author Marina Gergues
Rafijul Bari
Sharmila Koppisetti
Anna Gosiewska
Lin Kang
Robert J. Hariri
author_facet Marina Gergues
Rafijul Bari
Sharmila Koppisetti
Anna Gosiewska
Lin Kang
Robert J. Hariri
author_sort Marina Gergues
collection DOAJ
description Cellular senescence, a state of stable cell cycle arrest, acts as a double-edged sword in cancer biology. In young organisms, it acts as a barrier against tumorigenesis, but in the aging population, it may facilitate tumor growth and metastasis through the senescence-associated secretory phenotype (SASP). Natural killer (NK) cells play a critical role in the immune system, particularly in the surveillance, targeting, and elimination of malignant and senescent cells. However, age-related immunosenescence is characterized by declining NK cell function resulting in diminished ability to fight infection, eliminate senescent cells and suppress tumor development. This implies that preserving or augmenting NK cell function may be central to defense against age-related degenerative and malignant diseases. This review explores the underlying mechanisms behind these interactions, focusing on how aging influences the battle between the immune system and cancer, the implications of senescent NK cells in disease progression, and the potential of adoptive NK cell therapy as a countermeasure to these age-related immunological challenges.
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spelling doaj-art-2207926f65a14b1e998615030dfd1fe12025-08-20T03:07:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15652781565278Senescence, NK cells, and cancer: navigating the crossroads of aging and diseaseMarina GerguesRafijul BariSharmila KoppisettiAnna GosiewskaLin KangRobert J. HaririCellular senescence, a state of stable cell cycle arrest, acts as a double-edged sword in cancer biology. In young organisms, it acts as a barrier against tumorigenesis, but in the aging population, it may facilitate tumor growth and metastasis through the senescence-associated secretory phenotype (SASP). Natural killer (NK) cells play a critical role in the immune system, particularly in the surveillance, targeting, and elimination of malignant and senescent cells. However, age-related immunosenescence is characterized by declining NK cell function resulting in diminished ability to fight infection, eliminate senescent cells and suppress tumor development. This implies that preserving or augmenting NK cell function may be central to defense against age-related degenerative and malignant diseases. This review explores the underlying mechanisms behind these interactions, focusing on how aging influences the battle between the immune system and cancer, the implications of senescent NK cells in disease progression, and the potential of adoptive NK cell therapy as a countermeasure to these age-related immunological challenges.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565278/fullcellular senescenceNK cellsadoptive immunotherapyNK cell therapycancer
spellingShingle Marina Gergues
Rafijul Bari
Sharmila Koppisetti
Anna Gosiewska
Lin Kang
Robert J. Hariri
Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
Frontiers in Immunology
cellular senescence
NK cells
adoptive immunotherapy
NK cell therapy
cancer
title Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
title_full Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
title_fullStr Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
title_full_unstemmed Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
title_short Senescence, NK cells, and cancer: navigating the crossroads of aging and disease
title_sort senescence nk cells and cancer navigating the crossroads of aging and disease
topic cellular senescence
NK cells
adoptive immunotherapy
NK cell therapy
cancer
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1565278/full
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