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:Cytometry by Time-of-Flight for Profiling Therapeutic Response in Colorectal Cancer: Strengths, Limitations, and Translational Challenges.
Cytometry by Time-of-Flight for Profiling Therapeutic Response in Colorectal Cancer: Strengths, Limitations, and Translational Challenges.
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CyTOF 和 IMC 提供了可操作的生物标志物——包括 C1QC+巨噬细胞-T 细胞邻近度、HLA-DR 低单核细胞以及 NK 细胞成熟谱——这些标志物在影像学标准之外细化了疗效评估。要将这些发现应用于临床实践,需要抗体组合的标准化、前瞻性验证以及整合到临床工作流程中。
结直肠癌(CRC)的疗效评估仍主要依赖解剖学影像,而后者无法捕捉动态的免疫或基质适应。飞行时间流式细胞术(CyTOF)和成像质谱流式细胞术(IMC)等技术可实现高维单细胞蛋白质组学和空间分析,从而加深我们对CRC治疗反应的理解。本叙述性综述总结了来自人体、临床前和类器官研究的当前证据,描述了CyTOF和IMC如何被应用于表征CRC的治疗反应。
通过PubMed和主要肿瘤学期刊,识别了将悬浮CyTOF或IMC应用于CRC组织、血液或模型系统的相关出版物。优先考虑将单细胞特征与治疗反应或药效学联系起来的研究,并按生物学主题和临床适用性进行组织。
空间分析已识别出富含CD68 + CD74 +和C1QC +组织驻留巨噬细胞的巨噬细胞-T细胞生态位,其预测PD-1阻断获益比整体T细胞密度更准确。相反,癌相关成纤维细胞(CAF)致密基质和粒细胞邻近与耐药相关。系统性CyTOF研究已证明围手术期淋巴细胞减少、持续性HLA-DR低单核细胞,以及化疗诱导的成熟CD56 dim CD16 +自然杀伤(NK)细胞耗竭,背景为STAT5偏向。类器官和磷酸化信号研究表明,细胞分化状态决定致癌性ERK激活和治疗耐受性。总体而言,这些数据集勾勒出与免疫治疗和化疗相关的药效学和预测性生物标志物。
Relevant publications applying suspension CyTOF or IMC to CRC tissue, blood, or model systems were identified through PubMed and major oncology journals. Studies linking single-cell features to treatment response or pharmacodynamics were prioritized and organized by biological theme and clinical applicability.
Spatial analyses have identified macrophage-T-cell niches enriched for CD68 + CD74 + and C1QC + resident-tissue macrophages that predict benefit from PD-1 blockade more accurately than bulk T-cell density. Conversely, cancer-associated fibroblast (CAF)-dense matrices and granulocytic proximity associate with resistance. Systemic CyTOF studies have demonstrated peri-operative lymphopenia, persistent HLA-DR low monocytes, and chemotherapy-induced depletion of mature CD56 dim CD16 + natural killer (NK) cells on a STAT5-biased background. Organoid and phospho-signaling studies show that cellular differentiation states determine oncogenic ERK activation and therapy tolerance. Collectively, these datasets outline pharmacodynamic and predictive biomarkers relevant to immunotherapy and chemotherapy.
CyTOF and IMC provide actionable biomarkers - including C1QC + macrophage-T-cell proximity, HLA-DR low monocytes, and NK-cell maturation profiles - that refine response assessment beyond imaging criteria. Harmonization of antibody panels, prospective validation, and integration into clinical workflows are required to apply these findings in clinical practice.
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