Journal Article

DKFZ-2026-00193

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Defining the cellular and molecular identities of histologic subtypes in lung adenocarcinoma.

Lee, J. (First author)DKFZ* ; Jeong, J. Y. ; Hong, M. J. ; Choi, Y. H. ; Kim, J. Y. ; Lee, J. H. ; Choi, J. E. ; Kim, M. ; Do, Y. W. ; Lee, E. B. ; Choi, S. H. ; Yoo, S. S. ; Park, J. Y. ; Kim, J. K. ; Lee, S. Y.

2026
Biomed Central London

Abstract: 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.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.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.These findings deepen our understanding of the histologic heterogeneity of LUAD and may facilitate the development of subtype-specific biomarkers and targeted therapeutic strategies.

Keyword(s): Histologic subtypes ; Lung adenocarcinoma ; Spatial tanscriptomics ; scRNA-seq

Note: #EA:B270# / Volume 15, article number 12, (2026)

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Contributing Institute(s):

1. B270 Regulatorische Genomik und Evolution von Tumoren (B270)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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