{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:34:01Z","timestamp":1781105641376,"version":"3.54.1"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"16","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A27217"],"award-info":[{"award-number":["A27217"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UKRI | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X001075\/1"],"award-info":[{"award-number":["MR\/X001075\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["FC001112"],"award-info":[{"award-number":["FC001112"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UKRI | Medical Research Council","doi-asserted-by":"publisher","award":["FC001112"],"award-info":[{"award-number":["FC001112"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["FC001112"],"award-info":[{"award-number":["FC001112"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102126\/B\/13\/Z"],"award-info":[{"award-number":["102126\/B\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UKRI | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/V000659\/1"],"award-info":[{"award-number":["MR\/V000659\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:p>Metastatic breast cancer accounts for 7% of cancer-related deaths, with the lungs being a common site of cancer spread. In parallel, lower respiratory tract infections, including those caused by respiratory syncytial virus (RSV), remain a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce marked changes in the lung. However, how these changes influence metastasis initiation and cancer progression remains unclear. Using breast cancer and other cancer cell types in an experimental lung metastasis model, we show that RSV infection impairs tumor cell seeding and early growth in the lung, resulting in fewer metastatic nodules. We demonstrate that restriction of metastatic spread is due to alterations in the lung environment mediated by RSV-induced type I interferons (IFNs). Consistent with this idea, intranasal administration of recombinant IFN-\u03b1 is sufficient to recapitulate the anti-metastatic effect of RSV infection. Using single cell RNA sequencing supported by in vivo and ex vivo validation, we show that IFN-\u03b1 influences interactions between epithelial\/endothelial cells and cancer cells. Furthermore, both RSV infection and IFN-\u03b1 administration trigger marked local and systemic upregulation of Galectin-9, an IFN-inducible protein associated with acute respiratory infection in humans. Treatment of cancer cells with Galectin-9 alone is sufficient to restrict metastatic seeding. Altogether, our results suggest that type I IFNs induced by respiratory virus infection render the lungs less permissive to cancer cell seeding and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization.<\/jats:p>","DOI":"10.1073\/pnas.2412919123","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:47:18Z","timestamp":1776440838000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Type I interferons induced upon respiratory viral infection impair lung metastatic initiation"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6289-5060","authenticated-orcid":false,"given":"Ana","family":"Farias","sequence":"first","affiliation":[{"name":"Respiratory Infections Section, National Heart and Lung Institute, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L.","family":"Bridgeman","sequence":"additional","affiliation":[{"name":"Tumor-Host Interaction Laboratory, The Francis Crick Institute","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-8161","authenticated-orcid":false,"given":"Felipe S.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Tumor-Host Interaction Laboratory, The Francis Crick Institute","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2058-8521","authenticated-orcid":false,"given":"Franz","family":"Puttur","sequence":"additional","affiliation":[{"name":"Inflammation Repair and Development, National Heart and Lung Institute, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-1814","authenticated-orcid":false,"given":"Amber","family":"Owen","sequence":"additional","affiliation":[{"name":"Respiratory Infections Section, National Heart and Lung Institute, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5702-5918","authenticated-orcid":false,"given":"Stefanie","family":"Ruhland","sequence":"additional","affiliation":[{"name":"Tumor-Host Interaction Laboratory, The Francis Crick Institute","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rute M. M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Tumor-Host Interaction Laboratory, The Francis Crick Institute","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Regensburg","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-3311","authenticated-orcid":false,"given":"Ilaria","family":"Malanchi","sequence":"additional","affiliation":[{"name":"Tumor-Host Interaction Laboratory, The Francis Crick Institute","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6607-5000","authenticated-orcid":false,"given":"Cecilia","family":"Johansson","sequence":"additional","affiliation":[{"name":"Respiratory Infections Section, National Heart and Lung Institute, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"80","article-title":"What makes the lung unique\u2014Tissue-specific immunity in the respiratory tract","volume":"5","author":"Nobs S. P.","year":"2020","unstructured":"S. P. Nobs, What makes the lung unique\u2014Tissue-specific immunity in the respiratory tract. EMJ Respir. 5, 80\u201390 (2020).","journal-title":"EMJ Respir."},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11071010"},{"key":"e_1_3_4_3_2","unstructured":"World Health Organization Cancer. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer. Accessed 3 February 2025."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_3_4_5_2","unstructured":"World Health Organisation The top 10 causes of death. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/the-top-10-causes-of-death. Accessed 7 August 2024."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0051-2022"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7229a4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11111324"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l5021"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab491"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws151"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201402-0338OC"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09332-0"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.592891"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1260776"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00333-14"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00259"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052206"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804089"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904022116"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140825"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3845"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology10090856"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-031920-093932"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0065"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11121943"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep18533"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-019-0190-0"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1234571"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058913"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00571-6"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00304"},{"key":"e_1_3_4_33_2","first-page":"4697","article-title":"Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice","volume":"1950","author":"Mack M.","year":"2001","unstructured":"M. Mack , Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. J. Immunol. Baltim. Md. 1950, 4697\u20134704 (2001).","journal-title":"J. Immunol. Baltim. Md."},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02313-07"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1159\/000446824"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.032"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910340321"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01585083"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1988.217"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10694"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.11.025"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00336-7"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2024.05.020"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1487-6"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.04.007"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0474-3"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40588-019-0111-8"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2877-5"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2014.10.011"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020430"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0861"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1075-122X.2006.00334.x"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwn062"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clicom.2025.05.002"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.232.263"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111713"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1008-1091"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1025"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01045-4"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16140"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aav7638"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.505"},{"key":"e_1_3_4_63_2","unstructured":"V. Bridgeman I. Malanchi A. Farias C. Johansson Type I interferons induced upon RSV infection change the lung microenvironment and impair seeding of lung metastatic breast cancer cells. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE303448. Deposited 23 July 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2412919123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:47:43Z","timestamp":1776440863000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2412919123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":63,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,4,21]]}},"alternative-id":["10.1073\/pnas.2412919123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2412919123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]},"assertion":[{"value":"2024-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2412919123"}}