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Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of\n                    <jats:italic>PTEN<\/jats:italic>\n                    , a tumor suppressor, in human non\u2013small cell lung cancers (NSCLC). Here, we show that constitutive expression of human\n                    <jats:italic>MAGE-A4<\/jats:italic>\n                    with\n                    <jats:italic>Pten<\/jats:italic>\n                    loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA\n                    <jats:sup>+<\/jats:sup>\n                    CD138\n                    <jats:sup>+<\/jats:sup>\n                    CXCR4\n                    <jats:sup>+<\/jats:sup>\n                    plasma cells (PCs) and increased expression of CXCL12 in endothelial cells. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138\n                    <jats:sup>+<\/jats:sup>\n                    IgA\n                    <jats:sup>+<\/jats:sup>\n                    PCs surrounding tumors. Abrogation of PCs decreased tumor burden, increased activated T cell infiltration, and reduced CD163\n                    <jats:sup>+<\/jats:sup>\n                    CD206\n                    <jats:sup>+<\/jats:sup>\n                    macrophages in the MAGE-A4\u2013induced lung tumors. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA\n                    <jats:sup>+<\/jats:sup>\n                    PCs in the lungs.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ads4227","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T13:58:36Z","timestamp":1739368716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["MAGE-A4 induces non\u2013small cell lung cancer and tumor-promoting plasma cell accumulation"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-0911","authenticated-orcid":true,"given":"Dominique","family":"Armstrong","sequence":"first","affiliation":[{"name":"Translation Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3943-3044","authenticated-orcid":true,"given":"Cheng-Yen","family":"Chang","sequence":"additional","affiliation":[{"name":"Translation Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2123-3554","authenticated-orcid":true,"given":"Monica J.","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2499-8816","authenticated-orcid":true,"given":"Linda","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pathology, Michael E. 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