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Divergent CD45+ immune landscapes shape the lung tumor microenvironment

BackgroundThe lung tumor microenvironment (TME) plays a crucial role in the progression and metastasis of lung cancer. It consists of various cell types that interact in complex ways to influence tumor behavior. CD45+ cells, as a component of the TME, have complex and multifaceted roles in lung canc...

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Hauptverfasser: Dizdarević, Selma (VerfasserIn) , Wiegandt, René (VerfasserIn) , Weigert, Andreas (VerfasserIn) , Stiewe, Thorsten (VerfasserIn) , Eul, Bastian (VerfasserIn) , Guenther, Stefan (VerfasserIn) , Grimminger, Friedrich (VerfasserIn) , Seeger, Werner (VerfasserIn) , Pullamsetti, Soni Savai (VerfasserIn) , Looso, Mario (VerfasserIn) , Turkowski, Kati (VerfasserIn) , Savai, Rajkumar (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 09 February 2026
In: Frontiers in immunology
Year: 2026, Jahrgang: 17, Pages: 1-22
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1765833
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2026.1765833
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1765833/full
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Verfasserangaben:Selma Dizdarević, René Wiegandt, Andreas Weigert, Thorsten Stiewe, Bastian Eul, Stefan Guenther, Friedrich Grimminger, Werner Seeger, Soni Savai Pullamsetti, Mario Looso, Kati Turkowski and Rajkumar Savai
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Zusammenfassung:BackgroundThe lung tumor microenvironment (TME) plays a crucial role in the progression and metastasis of lung cancer. It consists of various cell types that interact in complex ways to influence tumor behavior. CD45+ cells, as a component of the TME, have complex and multifaceted roles in lung cancer. The balance between the anti-tumor and pro-tumor functions of CD45+ cells can significantly affect lung cancer outcomes. Understanding these roles is essential for developing targeted therapies that harness the beneficial effects of CD45+ cells while mitigating their harmful effects.MethodsWe performed single-cell RNA sequencing of sorted CD45+ immune cells from healthy lungs, orthotopic LLC1 tumors, and KrasLA2 (Kras) genetically engineered tumors. Analyses included immune composition, transcriptional programs, differentiation trajectories, metabolic states, and ligand-receptor-based intercellular communication networks.ResultsFour major immune compartments, B cells, T cells, NK cells, and macrophages, underwent model-specific remodeling. LLC1 tumors showed B cell expansion and T and NK cell reduction, with inflammatory, stress-response, and NF−κB/TNF-dominant programs. KrasLA2 tumors retained a balanced immune composition but exhibited metabolic rewiring, elevated antigen-presentation signatures, and selective intercellular signaling. Subclustering revealed specialized changes across B cell (resting, mature, pre-Bcr, late pro-B, plasma), T cell (Cd4+, Cd8+, memory, activated, Treg, Th17), NK cell (Fcgr3high, Fcgr3low, Xcl1+), and macrophage (Ace+, Bcr+, Ccr2+, Cd3+, metabolic, MHCII+) subsets. Ligand-receptor analyses highlighted dense inflammatory networks in LLC1 tumors versus metabolically tuned signaling in KrasLA2 tumors.ConclusionDistinct CD45+ immune landscapes, characterized by inflammatory suppression in LLC1 and metabolic adaptation in KrasLA2 tumors, shape lung tumor biology. This atlas identifies genotype-specific immune vulnerabilities with potential relevance for precision immunotherapy in non-small cell lung cancer.
Beschreibung:Im Titel ist das Plussymbol hochgestellt
Gesehen am 19.03.2026
Beschreibung:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1765833

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