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Wang, Q. ; Sun, N. ; Zhang, C.-Y. ; Kunzke, T. ; Zens, P.* ; Feuchtinger, A. ; Berezowska, S.* ; Walch, A.K.

Metabolic heterogeneity in tumor cells impacts immunology in lung squamous cell carcinoma.

OncoImmunology 14:2457797 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Metabolic processes are crucial in immune regulation, yet the impact of metabolic heterogeneity on immunological functions remains unclear. Integrating metabolomics into immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. To elucidate such insight in lung squamous cell carcinoma (LUSC), we analyzed 106 LUSC tumor tissues. We performed high-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to obtain spatial metabolic profiles, and immunohistochemistry to detect tumor-infiltrating T lymphocytes (TILs). Unsupervised k-means clustering and Simpson's diversity index were employed to assess metabolic heterogeneity, identifying five distinct metabolic tumor subpopulations. Our findings revealed that TILs are specifically associated with metabolite distributions, not randomly distributed. Integrating a validation cohort, we found that heterogeneity-correlated metabolites interact with CD8+ TIL-associated genes, affecting survival. High metabolic heterogeneity was linked to worse survival and lower TIL levels. Pathway enrichment analyses highlighted distinct metabolic pathways in each subpopulation and their potential responses to chemotherapy. This study uncovers the significant impact of metabolic heterogeneity on immune functions in LUSC, providing a foundation for tailoring therapeutic strategies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Immunology ; Spatial Metabolomics ; Lung Cancer ; Metabolic Heterogeneity ; Metabolic Tumor Subpopulation; Infiltrating T-cells; Cancer; Resistance; Microenvironment; Head; Immunometabolism; Mechanisms
ISSN (print) / ISBN 2162-4011
e-ISSN 2162-402X
Zeitschrift OncoImmunology
Quellenangaben Band: 14, Heft: 1, Seiten: , Artikelnummer: 2457797 Supplement: ,
Verlag Taylor & Francis
Verlagsort Philadelphia
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)
Förderungen Cancer Research Switzerland
Stiftung zur Krebsbekaempfung
Deutsche Krebshilfe
China Scholarship Council
Ministry of Education and Research of the Federal Republic of Germany
Deutsche Forschungsgemeinschaft