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:Innate lymphoid cells in pancreatic ductal adenocarcinoma: Immune regulation and therapeutic implications.
Innate lymphoid cells in pancreatic ductal adenocarcinoma: Immune regulation and therapeutic implications.
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在过去二十年中,免疫治疗通过将我们的策略转向利用机体自身免疫系统,彻底改变了癌症治疗格局,其前景在于通过控制和增强免疫反应的方法来抑制甚至消除肿瘤。胰腺导管腺癌(PDAC)是最致命的恶性肿瘤之一,其特点是存在免疫抑制性肿瘤免疫微环境(TIME),这是导致患者预后不良的核心因素。新兴研究揭示了固有淋巴样细胞(ILCs)作为组织驻留固有免疫枢纽,通过其动态可塑性、异质性以及与多种适应性免疫细胞的相互作用,在PDAC免疫调节中发挥双重作用。本综述系统总结了ILC亚群发育可塑性及其在PDAC中双向调控网络的最新研究进展,强调了靶向ILCs以重塑PDAC TIME的潜在价值。未来研究应整合单细胞多组学技术以解析ILCs的时空异质性,开发激活其抗肿瘤活性的策略,并探索将嵌合抗原受体(CAR)-NK细胞治疗与现有免疫治疗相结合的协同方案,为将PDAC从免疫“冷”肿瘤转化为免疫敏感肿瘤提供新范式。
Over the past two decades, immunotherapy has revolutionized cancer treatment by shifting our strategies to harness the body's own immune system, with the promise of inhibiting or even eliminating tumors through methods that control and enhance immune responses. Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, features an immunosuppressive tumor immune microenvironment (TIME) that serves as the core factor contributing to poor prognosis of patients. Emerging research has unveiled the dual role of innate lymphoid cells (ILCs), acting as tissue-resident innate immune hubs, in PDAC immune regulation through their dynamic plasticity, heterogeneity, and interactions with various adaptive immune cells.
This review systematically summarizes the latest research advancements in the developmental plasticity of ILC subsets and their bidirectional regulatory network in PDAC, highlighting the potential value of targeting ILCs to reshape the PDAC TIME.
Future research should integrate single-cell multi-omics technologies to dissect the spatiotemporal heterogeneity of ILCs, develop strategies to activate their anti-tumor activity, and explore synergistic approaches combining chimeric antigen receptor (CAR)-NK cell therapy with existing immunotherapies, providing new paradigms for transforming PDAC from an immunologically "cold" tumor to an immune-sensitive one.
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