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:Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.
Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.
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胰腺导管腺癌(PDAC)是一种侵袭性癌症,由于频繁复发、转移和治疗耐药,预后较差。导致这种耐药的一个主要因素是肿瘤抑制自然杀伤(NK)细胞的能力,而NK细胞是免疫系统对抗癌症的关键参与者。在PDAC中,肿瘤微环境(TME)创造了损害NK细胞功能的条件,包括增殖减少、细胞毒性减弱和肿瘤浸润受限。本综述探讨了肿瘤衍生因子、NK细胞和TME之间的相互作用如何促进肿瘤进展和治疗耐药。为应对这些挑战,我们提出了一种新的“三重NK细胞生物标志物方法”。该策略侧重于从三个关键领域识别生物标志物:肿瘤特征、TME因素和NK细胞抑制机制。这种方法可以指导个性化治疗以增强NK细胞活性。此外,我们强调了将基于NK细胞的疗法与传统治疗和药物重定位相结合以改善PDAC患者预后的潜力。尽管已取得进展,但仍需更多研究以更好地理解NK细胞功能障碍并开发有效疗法来克服这些障碍。
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes due to frequent recurrence, metastasis, and resistance to treatment. A major contributor to this resistance is the tumor's ability to suppress natural killer (NK) cells, which are key players in the immune system's fight against cancer. In PDAC, the tumor microenvironment (TME) creates conditions that impair NK cell function, including reduced proliferation, weakened cytotoxicity, and limited tumor infiltration.
This review examines how interactions between tumor-derived factors, NK cells, and the TME contribute to tumor progression and treatment resistance. To address these challenges, we propose a new "Triple NK Cell Biomarker Approach". This strategy focuses on identifying biomarkers from three critical areas: tumor characteristics, TME factors, and NK cell suppression mechanisms. This approach could guide personalized treatments to enhance NK cell activity.
Additionally, we highlight the potential of combining NK cell-based therapies with conventional treatments and repurposed drugs to improve outcomes for PDAC patients. While progress has been made, more research is needed to better understand NK cell dysfunction and develop effective therapies to overcome these barriers.
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