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Exp. Hematol. Oncol., Jan 23 2026, | https://doi.org/10.1186/s40164-025-00740-6
Defining the cellular and molecular identities of histologic subtypes in lung adenocarcinoma
Jusung Lee 1,7,8,9, Ji Yun Jeong 2,9, Mi Jeong Hong 3,9, Yoon Ha Choi 1, Ju Young Kim 1, Jang Hyuck Lee 3, Jin Eun Choi 3, Moonsik Kim 2, Young Woo Do 4, Eung Bae Lee 4, Sun Ha Choi 5, Seung Soo Yoo 5, Jae Yong Park 5, Jong Kyoung Kim 1,6,*, Shin YupLee 5,*
1Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
2Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
3Department of Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
4Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
5Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
6Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, Korea
7Division of Computational Genomics and System Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
8Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany
9These authors contributed equally
*Corresponding authors: correspondence to Jong Kyoung Kim or Shin YupLee
2Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
3Department of Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
4Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
5Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
6Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, Korea
7Division of Computational Genomics and System Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
8Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany
9These authors contributed equally
*Corresponding authors: correspondence to Jong Kyoung Kim or Shin YupLee
Abstract
Background
Tumor histology reflects disease aggressiveness and clinical outcomes in cancer patients. Lung adenocarcinomas (LUADs) are classified based on predominant histologic patterns, including high-grade micropapillary and solid subtypes which portend unfavorable clinical features and prognosis. However, the cellular and molecular characteristics underlying these histologic subtypes remain largely unknown.
Methods
We used scRNA-seq to profile 117,266 cells from 18 treatment-naïve LUADs with heterogeneous histologic patterns and also performed spatial transcriptomic analysis (10x Visium) for representative cases. By integrating single-cell transcriptomics with spatial information, we aimed to characterize the cellular identity and spatial organization driving LUAD heterogeneity.
Results
We demonstrated that histologic subtypes can be distinguished by subtype-specific cancer cell subpopulations and immunosuppressive phenotypes in the tumor microenvironment (TME). Our data reveal how intercellular interactions among cancer cells, macrophages, and CD8+ T cells in the prognostically unfavorable solid subtype are associated with cancer cell plasticity and promote an immunosuppressive TME. Additionally, we identify HMGA1 as a potential clinically relevant biomarker and therapeutic target for the solid subtype LUAD.
Conclusions
These findings deepen our understanding of the histologic heterogeneity of LUAD and may facilitate the development of subtype-specific biomarkers and targeted therapeutic strategies.
Tumor histology reflects disease aggressiveness and clinical outcomes in cancer patients. Lung adenocarcinomas (LUADs) are classified based on predominant histologic patterns, including high-grade micropapillary and solid subtypes which portend unfavorable clinical features and prognosis. However, the cellular and molecular characteristics underlying these histologic subtypes remain largely unknown.
Methods
We used scRNA-seq to profile 117,266 cells from 18 treatment-naïve LUADs with heterogeneous histologic patterns and also performed spatial transcriptomic analysis (10x Visium) for representative cases. By integrating single-cell transcriptomics with spatial information, we aimed to characterize the cellular identity and spatial organization driving LUAD heterogeneity.
Results
We demonstrated that histologic subtypes can be distinguished by subtype-specific cancer cell subpopulations and immunosuppressive phenotypes in the tumor microenvironment (TME). Our data reveal how intercellular interactions among cancer cells, macrophages, and CD8+ T cells in the prognostically unfavorable solid subtype are associated with cancer cell plasticity and promote an immunosuppressive TME. Additionally, we identify HMGA1 as a potential clinically relevant biomarker and therapeutic target for the solid subtype LUAD.
Conclusions
These findings deepen our understanding of the histologic heterogeneity of LUAD and may facilitate the development of subtype-specific biomarkers and targeted therapeutic strategies.
논문정보
- Research article
- 2026년 01월 (BRIC 등록일 2026-02-02)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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