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
使用逻辑门对 CAR 开关的组合靶抗原进行单细胞图谱分析
英文原题：Single-cell mapping of combinatorial target antigens for CAR switches using logic gates.
查看英文原题
Single-cell mapping of combinatorial target antigens for CAR switches using logic gates.
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中文摘要
识别能够区分癌细胞与周围正常组织细胞的最佳靶抗原，仍然是针对具有瘤内异质性的肿瘤进行嵌合抗原受体（CAR）细胞治疗的关键挑战。在本研究中，我们通过构建单细胞表达图谱，将组织复杂性解析到单个细胞水平，该图谱整合了来自412个肿瘤和12个正常器官的约140万个肿瘤细胞、肿瘤浸润正常细胞和参考正常细胞。我们采用随机森林和卷积神经网络的两步筛选方法，选择对区分单个恶性细胞与正常细胞贡献最大的基因对。基于配对基因在单个单细胞中的组合表达模式，评估了AND、OR和NOT逻辑门的肿瘤覆盖率和特异性。单细胞转录组偶联表位分析验证了在卵巢癌和结直肠癌中鉴定出的AND、OR和NOT开关靶点。
展开英文摘要原文
Identification of optimal target antigens that distinguish cancer cells from normal surrounding tissue cells remains a key challenge in chimeric antigen receptor (CAR) cell therapy for tumors with intratumoral heterogeneity. In this study, we dissected tissue complexity to the level of individual cells through the construction of a single-cell expression atlas that integrates ~1. 4 million tumor, tumor-infiltrating normal and reference normal cells from 412 tumors and 12 normal organs.
We used a two-step screening method using random forest and convolutional neural networks to select gene pairs that contribute most to discrimination between individual malignant and normal cells. Tumor coverage and specificity are evaluated for the AND, OR and NOT logic gates based on the combinatorial expression pattern of the pairing genes across individual single cells. Single-cell transcriptome-coupled epitope profiling validates the AND, OR and NOT switch targets identified in ovarian cancer and colorectal cancer.
论文信息
- 作者
- Kwon J、Kang J、Jo A、Seo K、An D、Baykan MY、Lee JH、Kim N
- 第一作者单位
- Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea.South Korea
- 通讯作者单位
- Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea. jungkyoon@kaist.ac.kr.South Korea
- 文献类型
- 非美国政府资助研究
- 期刊
- Nature biotechnology2023 Nov
- 原文标识
- PubMed 36797491 · DOI 10.1038/s41587-023-01686-y