Gergues Marina, Bari Rafijul, Koppisetti Sharmila, Gosiewska Anna, Kang Lin, Hariri Robert J
Research and Development, Celularity Inc., Florham Park, NJ, United States.
Front Immunol. 2025 Apr 4;16:1565278. doi: 10.3389/fimmu.2025.1565278. eCollection 2025.
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.
细胞衰老，即一种稳定的细胞周期停滞状态，在癌症生物学中犹如一把双刃剑。在年轻生物体中，它是抵御肿瘤发生的一道屏障，但在老龄群体中，它可能通过衰老相关分泌表型（SASP）促进肿瘤生长和转移。自然杀伤（NK）细胞在免疫系统中发挥着关键作用，尤其是在对恶性细胞和衰老细胞的监测、靶向及清除方面。然而，与年龄相关的免疫衰老的特征是NK细胞功能下降，导致抗感染、清除衰老细胞及抑制肿瘤发展的能力减弱。这意味着维持或增强NK细胞功能可能是抵御与年龄相关的退行性疾病和恶性疾病的核心。本综述探讨了这些相互作用背后的潜在机制，重点关注衰老如何影响免疫系统与癌症之间的对抗、衰老NK细胞在疾病进展中的影响，以及过继性NK细胞疗法作为应对这些与年龄相关的免疫挑战的对策的潜力。
