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 dissection of cervical cancer reveals key subsets of the tumor immune microenvironment.
Single-cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment.
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肿瘤微环境(TME)直接决定患者的预后和治疗效果。深入了解TME对于改善宫颈癌(CC)患者的预后至关重要。本研究对六对肿瘤及癌旁正常组织进行了单细胞RNA和TCR测序,以绘制CC免疫图谱。T细胞和NK细胞在肿瘤区域高度富集,并从细胞毒性表型向耗竭表型转变。我们的分析表明,细胞毒性大克隆T细胞是抗肿瘤反应中的关键效应细胞。本研究还揭示了与三级淋巴结构相关的肿瘤特异性生发中心B细胞。CC患者中生发中心B细胞比例高预示临床结局改善,并与激素免疫反应升高相关。我们描绘了免疫排斥的基质景观,并建立了肿瘤和基质细胞的联合模型来预测CC患者的预后。该研究揭示了TME中与抗肿瘤反应或预后相关的肿瘤生态系统亚群,并为未来的联合免疫治疗提供了信息。
The tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in-depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC).
This study conducted single-cell RNA and TCR sequencing of six-paired tumors and adjacent normal tissues to map the CC immune landscape. T and NK cells were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes.
Our analyses suggest that cytotoxic large-clone T cells are critical effectors in the antitumor response.
This study also revealed tumor-specific germinal center B cells associated with tertiary lymphoid structures. A high-germinal center B cell proportion in patients with CC is predictive of improved clinical outcomes and is associated with elevated hormonal immune responses.
We depicted an immune-excluded stromal landscape and established a joint model of tumor and stromal cells to predict CC patients' prognosis. The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME and provides information for future combinational immunotherapy.
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