Decoding the multicellular ecosystem of lung adenocarcinoma manifested as pulmonary subsolid nodules by single-cell RNA sequencing.

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.