[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-370265-105":59,"doc-detail-370265-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","mage-a4-induces-non-small-cell-lung-cancer-and-tumor-promoting-plasma-cell-accumulation","MAGE-A4 induces non-small cell lung cancer and tumor-promoting plasma cell accumulation","","Adaptive immunity is essential for tumor elimination, yet cancer-intrinsic mechanisms can bypass this control. Melanoma antigen-A4 (MAGE-A4) is a cancer-testis antigen expressed in solid tumors and linked to poor outcomes, but its role in cancer development and antitumor immunity is unclear. MAGE-A4 expression associates with PTEN loss in human NSCLC. Constitutive MAGE-A4 with Pten loss in mouse airway epithelia drives metastatic adenocarcinoma, enriched IgA+ CD138+ CXCR4+ plasma cells and higher endothelial CXCL12.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mage-a4-induces-non-small-cell-lung-cancer-and-tumor-promoting-plasma-cell-accumulation/370265/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mage-a4-induces-non-small-cell-lung-cancer-and-tumor-promoting-plasma-cell-accumulation/370265.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What relationship did the study find between MAGE-A4 expression and PTEN in non-small cell lung cancer?","Question",{"text":113,"@type":114},"MAGE-A4 expression was highly associated with loss of PTEN, a tumor suppressor, in human non-small cell lung cancers.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does MAGE-A4 with Pten loss affect tumor development in the mouse model?",{"text":118,"@type":114},"Constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia resulted in metastatic adenocarcinoma.",{"name":120,"@type":111,"acceptedAnswer":121},"What immune cell changes were observed in MAGE-A4–induced tumors?",{"text":122,"@type":114},"Tumors showed enrichment of IgA+ CD138+ CXCR4+ plasma cells and increased CXCL12 expression in endothelial cells; human NSCLC with MAGE-A4 also showed CD138+ IgA+ plasma cells surrounding tumors.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},370265,1790528260,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","CANCER  \nMAGE-A4 induces non–small cell lung cancer and tumor-promoting plasma cell accumulation  \nDominique Armstrong1,2, Cheng-Yen Chang1,2, Monica J. Hong2, Linda Green3, Yichao Shen4,5, William Hudson4,5, Kelsey E. Mauk2, Li-Zhen Song2, Sheetal Jammi2, Benjamin Casal2,  \nBrianna Burns6, Chad J. Creighton2,5, Alexandre Carisey7,8, Xiang H.-F. Zhang4,5, Neil J. McKenna4, Sung Wook Kang5,9, Hyun-Sung Lee5,9, William Decker5,6,  \nDavid B. Corry1,2,5,6,10,11, Farrah Kheradmand1,2,5,6,10,11*  \nAdaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. 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 PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of CXCL12 in endothelial cells. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138+ IgA+ PCs surrounding tumors. Abrogation of PCs decreased tumor burden, increased activated T cell infiltration, and reduced CD163+CD206+ macrophages in the MAGE-A4–induced lung tumors. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA+ PCs in the lungs.  \ncopyright © 2025 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S.  \nGovernment Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY-nc) .  \nINTRODUCTION  \nDespite the discovery of a growing number of targetable molecular markers associated with non–small cell lung cancer (NSCLC), minimal improvements have been made in the overall survival of patients with advanced disease (1). Small-molecule inhibitors targeting specific mutations have shown only limited short-term clinical efficacy (2, 3), and while immunotherapy has further improved outcomes in patients with lung cancer, the objective response rate in nonselected patients has remained low (4) . Checkpoint blockade has illuminated the interplay between malignant cells, their microenvironment, and the critical importance of the adaptive immune cells infiltrating tumors. Furthermore, several animal models of NSCLC using mutations commonly seen in patients (e.g., Kras, Egfr, Pten, Smad4, and Lkb1) have provided important advances in deciphering how individual mutations affect the tumor immune microenvironment (TIME) (5–9). However, the incomplete response rates of current therapies reveal an unmet need for a more comprehensive understanding of how additional tumor-specific factors alter their locoregional immune microenvironment (5) .  \nTumor-intrinsic factors such as cancer-testis antigens (CTAs) are expressed in several solid tumors and have been evaluated as  \n1translation Biology and Molecular Medicine Program, Baylor college of Medicine, houston,tX 77030, USA. 2department of Medicine, Baylor college of Medicine, houston, tX 77030, USA. 3department of Pathology, Michael e. deBakey vA, houston, tX 77030, USA. 4department of Molecular & cellular Biology, Baylor college of Medicine, houston, tX 77030, USA. 5dan l. duncan comprehensive cancer center, Baylor college of Medicine, houston, tX 77030, USA. 6department of Pathology and immunology, Baylor college of Medicine, houston, tX 77030, USA. 7department of Pediatrics, Baylor college of Medicine, houston, tX 77030, USA. 8William t Shearer center for human immunobiology, texas children’s hospital, houston, tX 77030, USA. 9 department of Surgery, Baylor college of Medicine, houston, tX 77030, USA. 10center for translational Research in infl","cbCair7QxuhqQIjz","https://ap.wps.com/l/cbCair7QxuhqQIjz","pdf",17771695,17,"English","# Introduction\n## Immune checkpoint therapy and tumor immune microenvironment\n## Cancer-testis antigens and MAGE-A4 in NSCLC\n# Study findings (MAGE-A4/PTEN and tumor promotion)\n## Plasma cell accumulation and CXCL12 signaling\n## Effects of abrogating plasma cells on tumor burden","[{\"question\":\"What relationship did the study find between MAGE-A4 expression and PTEN in non-small cell lung cancer?\",\"answer\":\"MAGE-A4 expression was highly associated with loss of PTEN, a tumor suppressor, in human non-small cell lung cancers.\"},{\"question\":\"How does MAGE-A4 with Pten loss affect tumor development in the mouse model?\",\"answer\":\"Constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia resulted in metastatic adenocarcinoma.\"},{\"question\":\"What immune cell changes were observed in MAGE-A4–induced tumors?\",\"answer\":\"Tumors showed enrichment of IgA+ CD138+ CXCR4+ plasma cells and increased CXCL12 expression in endothelial cells; human NSCLC with MAGE-A4 also showed CD138+ IgA+ plasma cells surrounding tumors.\"}]","MAGE-A4 induces non-small cell lung cancer and tumor-promoting plasma cell accumulation | PDF",1790187679,43]