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:Engineering immune-competent niches: strategies, applications, and translational hurdles in ovarian cancer organoid models.
Engineering immune-competent niches: strategies, applications, and translational hurdles in ovarian cancer organoid models.
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卵巢癌由于患者间高度异质性和免疫逃逸,仍然是最致命的妇科恶性肿瘤。传统的二维培养和动物模型无法维持肿瘤、免疫细胞和基质细胞之间的相互作用,在临床转化方面存在局限性。本综述讨论了利用成体干细胞(正常上皮、肿瘤组织和腹水)以及诱导多能干细胞构建类器官的方法,比较了从气液界面到微流控装置的各种培养平台。我们强调,包含免疫成分的类器官对于评估T细胞耗竭、NK细胞细胞毒性和基质通讯具有重要价值,有助于筛选免疫治疗、发现生物标志物和分析耐药性。持续存在的挑战包括血管化有限、免疫成分的短期维持以及缺乏标准化方案。我们提出了整合多组学、生物材料和自动化灌注的新解决方案,以提高生理保真度和可扩展性。总之,具有免疫微环境的卵巢癌类器官可以弥合临床前差距,加速个性化免疫治疗的开发。
Ovarian cancer remains the most lethal gynecologic malignancy due to strong interpatient heterogeneity and immune evasion. Traditional two-dimensional cultures and animal models lack the ability to maintain interactions among tumors, immune cells, and stromal cells and have limitations in clinical translation.
This review discusses the organoid construction methods using adult stem cells (normal epithelium, tumor tissues and ascites), and induced pluripotent stem cells, comparing various culture platforms from air-liquid interface to microfluidic devices.
We highlight organoids containing immune components are valuable for assessing T cell exhaustion, NK cell cytotoxicity, and stromal communication, which help to screen immunotherapy, discover biomarker, and profile drug resistance. The persistent challenges include limited vascularization, short-term maintenance of immune components and lack of standard protocols.
We present new solutions that integrate multi-omics, biomaterials and automated perfusion to improve physiological fidelity and scalability. Collectively, ovarian cancer organoids with immune microenvironment can bridge preclinical gaps and accelerate the development of personalized immune therapy.
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