腺癌
癌症研究
CD8型
病理
生物
肿瘤微环境
转录组
肺
恶性肿瘤
免疫系统
医学
癌症
免疫学
肿瘤细胞
内科学
基因表达
基因
生物化学
作者
Xin Zhang,Beibei Liang,Yuji Huang,Hua Meng,Zhiming Li,Junbao Du,L. Zhou,Yizhou Zhong,Bo Wang,Xiao Lin,Yu Guo,Xuewei Chen,Weicong Lu,Zhe‐Sheng Chen,Xingfen Yang,Zhenlie Huang
标识
DOI:10.1002/advs.202303753
摘要
The increased use of low-dose computed tomography screening has led to more frequent detection of early stage lung tumors, including minimally invasive adenocarcinoma (MIA). To unravel the intricacies of tumor cells and the immune microenvironment in MIA, this study performs a comprehensive single-cell transcriptomic analysis and profiles the transcriptomes of 156,447 cells from fresh paired MIA and invasive adenocarcinoma (IA) tumor samples, peripheral blood mononuclear cells, and adjacent normal tissue samples from three patients with synchronous multiple primary lung adenocarcinoma. This study highlights a connection and heterogeneity between the tumor ecosystem of MIA and IA. MIA tumor cells exhibited high expression of aquaporin-1 and angiotensin II receptor type 2 and a basal-like molecular character. Furthermore, it identifies that cathepsin B+ tumor-associated macrophages may over-activate CD8+ T cells in MIA, leading to an enrichment of granzyme K+ senescent CD8+ T cells, indicating the possibility of malignant progression behind the indolent appearance of MIA. These findings are further validated in 34 MIA and 35 IA samples by multiplexed immunofluorescence. These findings provide valuable insights into the mechanisms that maintain the indolent nature and prompt tumor progression of MIA and can be used to develop more effective therapeutic targets and strategies for MIA patients.
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