biostudies-literatureUnknown5(4)Deng YNational Key Research and Development Program of China Stem Cell and Translational ResearchNational Natural Science Foundation of ChinaLung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8⁺ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8⁺ T cCell reports. Medicine101489https://www.ebi.ac.uk/biostudies/studies/S-EPMC11031428biostudies-literatureMulticellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.PMC11031428Lai HZhang GDeng SMa LHu YLiu LZhang JZhu YGan FWang MLiu YLiu ZXia LLiao HCheng QWei SChen YShen SGuo CDeng YYuan YKang RChen LZha ZLi KBai YYuan GPu QYang ZYang YLuo LMei JLin FLiu CfalseMulticellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8⁺ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8⁺ T c2024-01-01T00:00:00Z2024 Apr2026-05-29T12:37:35.47Z2026-04-08T04:46:16.21ZS-EPMC110314283855470510.1016/j.xcrm.2024.101489