MAGE-A4 induces non-small cell lung cancer and tumor-promoting plasma cell accumulation.

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 , a tumor suppressor, in human non-small cell lung cancers (NSCLC). Here, we show that constitutive expression of human with 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 CD163CD206 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.