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:Mass cytometric single cell immune profiles of peripheral blood from acute myeloid leukemia patients in complete remission with measurable residual disease.
Mass cytometric single cell immune profiles of peripheral blood from acute myeloid leukemia patients in complete remission with measurable residual disease.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
约四分之一急性髓系白血病(AML)化疗应答者可检测到可测量残留病(MRD),MRD可预测复发和生存期缩短。研究者认为,免疫系统控制残留病可预防复发,但相关机制尚未充分阐明。本文采用质谱流式细胞术及42种抗体面板,对外周血进行单细胞免疫分析,重点关注细胞免疫应答标志物。比较6名健康供者与4名处于首次完全缓解且MRD阳性(CR1 MRD+)的AML患者。4名患者中3名具有有利遗传风险特征,另1名患者风险不良(复杂核型、TP53突变)且MRD水平较高。研究采用自组织映射进行无监督聚类,并通过降维分析展示和分析免疫细胞亚群。与健康供者相比,患者中CD57阳性NK细胞亚群比例较低。患者T细胞和NK细胞的活性及成熟标志物(CD44、颗粒酶B和磷酸化STAT5 Y694)表达均升高。尽管质谱流式细胞术成本较高且可扩展性有限,数据提示可采用42重标志物分析对全血细胞免疫进行监测,未来也可能作为临床试验的生物标志物平台。研究结果支持进一步开展CR1 MRD阳性AML患者的单细胞免疫分析研究。
Measurable residual disease (MRD) is detected in approximately a quarter of AML chemotherapy responders, serving as a predictor for relapse and shorter survival. Immunological control of residual disease is suggested to prevent relapse, but the mechanisms involved are not fully understood.
We present a peripheral blood single cell immune profiling by mass cytometry using a 42-antibody panel with particular emphasis on markers of cellular immune response. Six healthy donors were compared with four AML patients with MRD (MRD + ) in first complete remission (CR1 MRD+ ). Three of four patients demonstrated a favorable genetic risk profile, while the fourth patient had an unfavorable risk profile (complex karyotype, TP53-mutation) and a high level of MRD. Unsupervised clustering using self-organizing maps and dimensional reduction analysis was performed for visualization and analysis of immune cell subsets.
CD57 + natural killer (NK)-cell subsets were found to be less abundant in patients than in healthy donors. Both T and NK cells demonstrated elevated expression of activity and maturation markers (CD44, granzyme B, and phosho-STAT5 Y694) in patients.
Although mass cytometry remains an expensive method with limited scalability, our data suggest the utility for employing a 42-plex profiling for cellular immune surveillance in whole blood, and possibly as a biomarker platform in future clinical trials. The findings encourage further investigations of single cell immune profiling in CR1 MRD+ AML-patients.
MEMBER ACCOUNT
登录成功会直接打开下一页。