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 Profiling of the Immune Atlas of Tumor-Infiltrating Lymphocytes in Endometrial Carcinoma.
Single-Cell Profiling of the Immune Atlas of Tumor-Infiltrating Lymphocytes in Endometrial Carcinoma.
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子宫内膜癌(EC)是一种高发病率的妇科恶性肿瘤;然而,关于EC中TIL(肿瘤浸润淋巴细胞)群体的深入研究尚缺乏。我们旨在通过单细胞RNA测序(scRNA-seq)、质谱流式和流式细胞术分析,绘制I型EC中TIL的免疫图谱。
我们发现自然杀伤(NK)细胞和CD8+ T淋巴细胞是EC患者TIL的主要组成部分。我们首次鉴定了三个转录上不同的NK细胞亚群,它们可能具有多样的抗肿瘤功能。
此外,CD103+细胞对CD8+ T细胞群体有显著贡献。CD103+ CD8+ T细胞的标志性基因表达表明该细胞亚群具有组织驻留、免疫记忆和耗竭特性,被定义为组织驻留记忆T细胞(T RM细胞)。
此外,基于scRNA-seq和质谱流式分析,我们首次鉴定了CD103+ CD8+ T细胞的内在异质性,这些细胞被认为具有不同的细胞毒性、细胞黏附和耗竭状态功能。
总体而言,发现了不同的NK细胞亚群,可能为未来的研究提供启示。CD103+ CD8+ T细胞群体可能是EC中的一个重要免疫治疗靶点,针对该细胞群体联合免疫抑制治疗可能提高EC免疫治疗的疗效。
Endometrial carcinoma (EC) is a gynecological malignancy with a high incidence; however, thorough studies on tumor-infiltrating lymphocyte (TIL) populations in EC are lacking.
We aimed to map the immune atlas of TILs in type I EC via single-cell RNA sequencing (scRNA-seq), mass cytometry and flow cytometry analysis.
We found that natural killer (NK) cells and CD8+ T lymphocytes were the major components of TILs in EC patients.
We first identified three transcriptionally distinct NK cell subsets, which are likely to possess diverse anti-tumor functions.
Additionally, CD103+ cells substantially contributed to the CD8+ T cell population. The signature gene expression of CD103+ CD8+ T cells indicated the tissue residency, immunological memory, and exhaustion properties of this cell subset, which were defined as tissue-resident memory T cells (T RM cells).
Moreover, based on scRNA-seq and mass cytometry analysis, we first identified the intrinsic heterogeneity of CD103+ CD8+ T cells that were thought to have a distinct cytotoxicity, cell adhesion and exhaustion status functions. Collectively, distinct subsets of NK cells were found and might shed light on future investigations. CD103+ CD8+ T cell population may be an important immunotherapeutic target in EC and targeting this cell population with combined immunosuppressive therapy might improve the efficacy of immunotherapy for EC.
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