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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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Main Authors: Dizdarević, Selma (Author) , Wiegandt, René (Author) , Weigert, Andreas (Author) , Stiewe, Thorsten (Author) , Eul, Bastian (Author) , Guenther, Stefan (Author) , Grimminger, Friedrich (Author) , Seeger, Werner (Author) , Pullamsetti, Soni Savai (Author) , Looso, Mario (Author) , Turkowski, Kati (Author) , Savai, Rajkumar (Author)
Format: Article (Journal)
Language:English
Published: 09 February 2026
In: Frontiers in immunology
Year: 2026, Volume: 17, Pages: 1-22
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1765833
Online Access: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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Author Notes: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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Summary: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.
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Gesehen am 19.03.2026
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1765833

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