Publication Date
2-14-2025
Journal
Science Advances
DOI
10.1126/sciadv.ads4227
PMID
39937892
PMCID
PMC11817953
PubMedCentral® Posted Date
2-12-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Antigens, Neoplasm, Humans, Carcinoma, Non-Small-Cell Lung, Animals, Lung Neoplasms, Plasma Cells, Neoplasm Proteins, Mice, Cell Line, Tumor, PTEN Phosphohydrolase
Abstract
Adaptive 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.
Included in
Immunology of Infectious Disease Commons, Immunopathology Commons, Medical Immunology Commons, Pathology Commons
