{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:57:53Z","timestamp":1787504273071,"version":"build-2736575974"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,9]]},"abstract":"<jats:p>\n                    The cellular and molecular components required for the formation of premetastatic niche (PMN) to promote lung metastasis need to be further investigated. Lung epithelial cells have been reported to exhibit immunomodulatory roles in lung homeostasis and also to mediate immunosuppressive PMN formation in lung metastasis. Here, by single-cell sequencing, we identified a tumor-polarized subpopulation of alveolar type 2 (AT2) epithelial cells with increased expression of glutathione peroxidase 3 (GPX3) and high production of interleukin (IL)-10 in the PMN. IL-10-producing GPX3\n                    <jats:sup>+<\/jats:sup>\n                    AT2 cells inhibited CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell proliferation but enhanced regulatory T cell generation. Mechanistically, tumor exosome-inducing GPX3 expression is required for GPX3\n                    <jats:sup>+<\/jats:sup>\n                    AT2 cells to preferentially produce IL-10 by stabilizing hypoxia-inducible factor 1 (HIF-1\u03b1) and promoting HIF-1\u03b1-induced IL-10 production. Accordingly, conditional knockout of GPX3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models. Together, our findings reveal a role of tumor-polarized GPX3\n                    <jats:sup>+<\/jats:sup>\n                    AT2 cells in promoting lung PMN formation, adding insights into immune evasion in lung metastasis and providing potential targets for the intervention of tumor metastasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2201899119","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T15:22:29Z","timestamp":1659367349000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Tumor-polarized GPX3\n                    <sup>+<\/sup>\n                    AT2 lung epithelial cells promote premetastatic niche formation"],"prefix":"10.1073","volume":"119","author":[{"given":"Zixin","family":"Wang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai 200433, China"},{"name":"Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9018-9972","authenticated-orcid":false,"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6720-4732","authenticated-orcid":false,"given":"Ziqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetao","family":"Cao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai 200433, China"},{"name":"Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Medical Immunology, Institute of Immunology, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1130"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.6"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.11.016"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0309-y"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04186"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15756"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1101-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.09.011"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114630"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16985"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10138"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0959-5"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0520"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.06.021"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811717115"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68782"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3739"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.53"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3150"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082197"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041717"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0465"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113224"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.03.019"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.146290"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-375014"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2701"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00051"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.011"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.028"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3726"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02683-x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0029-z"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.047"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201601026"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002991"},{"key":"e_1_3_4_42_2","unstructured":"Y. Gu Z. Wang Single-cell transcriptome of tumor-educated lung epithelial cells. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE195754. Deposited 21 July 2022."},{"key":"e_1_3_4_43_2","unstructured":"Y. Gu Z. Wang Transcriptome sequencing of tumor-educated lung epithelial cells in the pre-metastatic niche. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE195755. Deposited 21 July 2022."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2201899119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T15:26:34Z","timestamp":1659367594000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2201899119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":43,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2022,8,9]]}},"alternative-id":["10.1073\/pnas.2201899119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2201899119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"2022-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2201899119"}}