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Incidence of non\u2010smoking associated lung cancer is rising rapidly, globally. Global epidemiology supports an association between lung cancer incidence and consumption of bovine products. The search for meat\u2010\/milk\u2010associated cancer risk factors led to the isolation of plasmid DNA termed Bovine Meat and Milk Factors (BMMFs). Due to detection of increased expression levels of a conserved BMMF\u2010encoded protein (Rep) in tissues of colorectal cancer patients, BMMFs have been proposed as causal risk factors for cancer acting via inflammation\u2010driven indirect carcinogenesis. Yet, their presence and possible contribution to lung cancer remained elusive. In this study, Rep expression was quantified in paired tumor\/peritumor tissues from lung cancer patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200935) as well as cancer\u2010free individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919, tissues adjacent to benign hamartoma) by immunohistochemistry, co\u2010immunofluorescence microscopy, immunodetection\/mass spectroscopy and genomics\/transcriptomics screening. In all patients tested, Rep expression was immunohistochemically observed in CD68\n                    <jats:sup>+<\/jats:sup>\n                    CD163\n                    <jats:sup>+<\/jats:sup>\n                    alveolar lung macrophages, which were present at higher numbers in peritumor tissues of cancer patients compared to controls. Expression was inversely correlated with smoking intensity, supporting BMMFs' function as a new, smoking\u2010independent biomarker and possible driver for lung cancer. BMMF\n                    <jats:sup>+<\/jats:sup>\n                    macrophages revealed a cancer\u2010promoting M2\u2010like phenotype upon scRNA\u2010seq, suggesting BMMF as target for both prevention and therapy. BMMFs might contribute to lung cancer by inducing pro\u2010tumorigenic macrophage populations and serve as marker for (early) cancer detection and prevention.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70574","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:23:03Z","timestamp":1780374183000},"page":"2036-2053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung Cancer Patients Display Increased Expression of Bovine Meat and Milk Factor (\n                    <scp>BMMF<\/scp>\n                    ) Proteins in Peritumor Alveolar Macrophages"],"prefix":"10.1002","volume":"159","author":[{"given":"Nives","family":"Cecere","sequence":"first","affiliation":[{"name":"Division of Episomal\u2010Persistent DNA in Cancer\u2010 and Chronic Diseases German Cancer Research Center (DKFZ)  Heidelberg 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German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunjan","family":"Shukla","sequence":"additional","affiliation":[{"name":"Division of Episomal\u2010Persistent DNA in Cancer\u2010 and Chronic Diseases German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Frehtman","sequence":"additional","affiliation":[{"name":"Biopharmaceutical Production and Development Unit German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tessmer","sequence":"additional","affiliation":[{"name":"Core Facility Antibodies German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Eichhorn","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Thoraxklinik at Heidelberg University Hospital  Heidelberg Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Allg\u00e4uer","sequence":"additional","affiliation":[{"name":"Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL)  Heidelberg Germany"},{"name":"Department of Pathology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Brobeil","sequence":"additional","affiliation":[{"name":"Department of Pathology Heidelberg University Hospital  Heidelberg Germany"},{"name":"Tissue Bank of the National Center for Tumor Diseases (NCT)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Core 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