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:Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer.
Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer.
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早发性宫颈癌(EOCC)和晚发性宫颈癌(LOCC)代表两种临床上不同的亚型,各自具有独特的临床表现和治疗反应。然而,它们的免疫学特征仍鲜有探索。在此,我们分析了4例EOCC和4例LOCC样本的单细胞转录组数据,以比较其免疫结构。EOCC中的上皮细胞表现出显著的双重免疫表型,其特征是由CXCL产生增加驱动的免疫抑制特性,同时伴有与HLA分子表达升高相关的免疫刺激特征。LOCC中的CD4+和CD8+T细胞表现出增强的活化状态,而NK细胞则表现出减弱的细胞毒性。LOCC中的巨噬细胞显示出向M1和M2表型增强的极化,同时树突状细胞表现出增强的抗原呈递能力。关于癌相关成纤维细胞(CAFs),EOCC富含炎症性CAFs,而LOCC则含有更高比例的抗原呈递CAFs。这些发现揭示了EOCC与LOCC之间多方面的免疫异质性,强调了制定年龄定制免疫治疗策略的必要性。
Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses.
However, their immunological profiles remain poorly explored.
Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures. Epithelial cells in EOCC exhibited a notable dual immunological phenotype, characterized by immune-suppressive properties driven by elevated CXCL production, alongside immune-stimulatory features linked to heightened HLA molecule expression.
CD4 + and CD8 + T cells in LOCC demonstrated a heightened activation state, while NK cells exhibited diminished cytotoxicity. Macrophages in LOCC displayed enhanced polarization towards both M1 and M2 phenotypes, along with dendritic cells showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), EOCC was enriched with inflammatory CAFs, whereas LOCC harbored a higher proportion of antigen-presenting CAFs.
These findings reveal the multifaceted immune heterogeneity between EOCC and LOCC, underscoring the imperative for age-tailored immunotherapeutic strategies.
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