Xing Xudong, Yang Fan, Huang Qi, Guo Haifa, Li Jiawei, Qiu Mantang, Bai Fan, Wang Jun
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Tsinghua University, Beijing 100084, China.
Sci Adv. 2021 Jan 27;7(5). doi: 10.1126/sciadv.abd9738. Print 2021 Jan.
Lung adenocarcinomas (LUAD) that radiologically display as subsolid nodules (SSNs) exhibit more indolent biological behavior than solid LUAD. The transcriptomic features and tumor microenvironment (TME) of SSN remain poorly understood. Here, we performed single-cell RNA sequencing analyses of 16 SSN samples, 6 adjacent normal lung tissues (nLung), and 9 primary LUAD with lymph node metastasis (mLUAD). Approximately 0.6 billion unique transcripts were obtained from 118,293 cells. We found that cytotoxic natural killer/T cells were dominant in the TME of SSN, and malignant cells in SSN undergo a strong metabolic reprogram and immune stress. In SSN, the subtype composition of endothelial cells was similar to that in mLUAD, while the subtype distribution of fibroblasts was more like that in nLung. Our study provides single-cell transcriptomic profiling of SSN and their TME. This resource provides deeper insight into the indolent nature of SSN and will be helpful in advancing lung cancer immunotherapy.
在放射学上表现为亚实性结节（SSN）的肺腺癌（LUAD）比实性LUAD具有更惰性的生物学行为。SSN的转录组特征和肿瘤微环境（TME）仍知之甚少。在此，我们对16个SSN样本、6个相邻正常肺组织（nLung）和9个伴有淋巴结转移的原发性LUAD（mLUAD）进行了单细胞RNA测序分析。从118,293个细胞中获得了约6亿个独特转录本。我们发现细胞毒性自然杀伤/T细胞在SSN的TME中占主导地位，并且SSN中的恶性细胞经历了强烈的代谢重编程和免疫应激。在SSN中，内皮细胞的亚型组成与mLUAD中的相似，而成纤维细胞的亚型分布更类似于nLung中的。我们的研究提供了SSN及其TME的单细胞转录组图谱。这一资源为深入了解SSN的惰性本质提供了帮助，并将有助于推进肺癌免疫治疗。
