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Association of tumour-associated macrophage states with non-conserved lncrnas in lung cancer

Genes & Immunity (2026)Cite this article

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Abstract

Tumour-associated macrophages (TAMs) are central players in the tumour microenvironment, driving cancer progression and modulating immune responses. Renowned for their ability to rapidly adapt to environmental changes, TAMs can adopt a wide range of functional phenotypes. However, the regulatory mechanisms underlying this functional plasticity are still not fully understood. Long non-coding RNAs (lncRNAs), as key regulators of epigenetic and post-transcriptional processes, are increasingly recognized for their potential role in TAM polarization. In this study, we conducted a comprehensive comparative analysis of lncRNA expression in TAMs derived from both mouse and human lung carcinomas. Although we identified a small group of murine lncRNAs as potential human orthologs through orthogonal in silico approaches, the majority of murine lncRNAs lacked clear human equivalents. Overall, our findings reveal distinct lncRNA expression patterns in lung carcinoma mouse and human TAMs, underscoring the importance of utilizing human-based models to thoroughly investigate the roles of lncRNAs in immune regulation and bridge the translational gap between murine and human cancer immunology.

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Fig. 1: LncRNAs in MHC-IIlow andhigh TAMs exhibit significant differential gene expression.
Fig. 2: Conserved short sequence stretches in lncRNAs between mouse and human.
Fig. 3: LncRNAs in TAMs have limited functional conservation between mouse and human.

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Data availability

Sequencing data have been deposited to GEO database with accession number GSE302249.

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Acknowledgements

This project was funded by C1 Interne Fondsen KU Leuven/ C1 Internal Funds KU Leuven (C16/19/006). S. Cinque was the recipient of FWO– Flanders research organization PhD fellowship (1SD1620N). Y. Verheyden is the recipient of an FWO – Flanders research organization PhD fellowship (1SC5122N).

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Authors and Affiliations

  1. Laboratory for RNA Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium

    Yvessa Verheyden, Sonia Cinque & Eleonora Leucci

  2. Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium

    Daliya Kancheva & Jo A. Van Ginderachter

  3. Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium

    Daliya Kancheva & Jo A. Van Ginderachter

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  1. Yvessa Verheyden
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YV: conceptualization, data curation, data analysis, investigation, visualization, methodology, writing original draft. SC: methodology. DK: data analysis. JVG: conceptualization, editing. EL: conceptualisation, supervision, funding acquisition, writing original draft.

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Correspondence to Eleonora Leucci.

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The experiments involving animals have been conducted according to the guidelines of the Belgian Council for Laboratory Animal Science and were approved by the Ethical Committee for Animal Experiments of the Vrije Universiteit Brussel (ECD number 16-220-2).

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Verheyden, Y., Cinque, S., Kancheva, D. et al. Association of tumour-associated macrophage states with non-conserved lncrnas in lung cancer. Genes Immun (2026). https://doi.org/10.1038/s41435-026-00377-3

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