RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Senescence, NK cells, and cancer: navigating the crossroads of aging and disease.
Senescence, NK cells, and cancer: navigating the crossroads of aging and disease.
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细胞衰老是一种稳定的细胞周期停滞状态,在癌症生物学中具有双重作用。在年轻个体中,它可形成抵御肿瘤发生的屏障;而在老年群体中,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关键作用,尤其参与监视、靶向和清除恶性及衰老细胞。然而,年龄相关免疫衰老的特点是NK细胞功能下降,导致抗感染、清除衰老细胞及抑制肿瘤发生的能力减弱。这提示,维持或增强NK细胞功能可能是抵御年龄相关退行性疾病和恶性疾病的核心。本综述探讨这些相互作用背后的机制,重点关注衰老如何影响免疫系统与癌症的博弈、衰老NK细胞对疾病进展的影响,以及过继NK细胞疗法应对年龄相关免疫挑战的潜力。
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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