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:Deep phenotyping of surface stimulatory and inhibitory co-receptors on cancer-resident T and NK cells reveals cell subsets within the tumor-reactive CTL population that are uniquely defined by NKG2A expression.
Deep phenotyping of surface stimulatory and inhibitory co-receptors on cancer-resident T and NK cells reveals cell subsets within the tumor-reactive CTL population that are uniquely defined by NKG2A expression.
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免疫肿瘤学(IO)领域正在发展,利用能够共同靶向多个细胞表面刺激性和抑制性共受体(SICR)的新型抗体骨架。这种方法需要更好地理解IO相关肿瘤浸润白细胞(TIL)细胞类型(如T细胞和自然杀伤(NK)细胞)在单细胞水平上的SICR共表达。利用高维流式细胞术,我们针对多种人类实体瘤中肿瘤驻留T细胞和NK细胞建立了全面的SICR图谱,这些肿瘤明确需要改进的免疫治疗干预。借助我们大型流式panel的强大功能,我们对关键的CD8 + CD39 + 细胞毒性T淋巴细胞(CTL)群体进行了深度表型分析,该群体富集了肿瘤反应性细胞毒性细胞,揭示了按其SICR谱区分的亚群,其中包括三个由NKG2A表达独特定义的亚群。本研究为人类TIL T细胞和NK细胞建立了全面的SICR表型,为指导下一代IO分子的设计和应用提供了见解。
The field of Immuno-Oncology (IO) is evolving to utilise novel antibody backbones that can co-target multiple cell-surface stimulatory and inhibitory co-receptors (SICR). This approach necessitates a better understanding of SICR co-expression at the single-cell level on IO-relevant tumor-infiltrating leukocyte (TIL) cell types such as T and natural killer (NK) cells.
Using high-dimensional flow cytometry we established a comprehensive SICR profile for tumor-resident T and NK cells across a range of human solid tumors where there is a clear need for improved immunotherapeutic intervention. Leveraging the power of our large flow panel, we performed deep-phenotyping of the critical CD8 + CD39 + Cytotoxic T Lymphocyte (CTL) population that is enriched for tumor-reactive cytotoxic cells, revealing subsets that are differentiated by their SICR profile, including three that are uniquely defined by NKG2A expression.
This study establishes a comprehensive SICR phenotype for human TIL T and NK cells, providing insights to guide the design and application of the next generation of IO molecules.
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