2. Academic Validation
  3. 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

  • Sci Adv. 2025 Feb 14;11(7):eads4227. doi: 10.1126/sciadv.ads4227.
Dominique Armstrong 1 2,  Cheng-Yen Chang 1 2,  Monica J Hong 2,  Linda Green 3,  Yichao Shen 4 5,  William Hudson 4 5,  Kelsey E Mauk 2,  Li-Zhen Song 2,  Sheetal Jammi 2,  Benjamin Casal 2,  Brianna Burns 6,  Chad J Creighton 2 5,  Alexandre Carisey 7 8,  Xiang H-F Zhang 4 5,  Neil J McKenna 4,  Sung Wook Kang 5 9,  Hyun-Sung Lee 5 9,  William Decker 5 6,  David B Corry 1 2 5 6 10 11,  Farrah Kheradmand 1 2 5 6 10 11
Affiliations

Affiliations

  • 1 Translation Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, TX 77030, USA.
  • 2 Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • 3 Department of Pathology, Michael E. DeBakey VA, Houston, TX 77030, USA.
  • 4 Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • 5 Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • 6 Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
  • 7 Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
  • 8 William 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.
  • 10 Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey VA, Houston, TX 77030, USA.
  • 11 Biology of Inflammation Center, Baylor College of Medicine, Houston, TX 77030, USA.
PMID: 39937892 DOI: 10.1126/sciadv.ads4227
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.

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