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 <i>PTEN</i>, a tumor suppressor, in human non-small cell lung cancers (NSCLC). Here, we show that constitutive expression of human <i>MAGE-A4</i> with <i>Pten</i> loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA<sup>+</sup> CD138<sup>+</sup> CXCR4<sup>+</sup> plasma cells (PCs) and increased expression of CXCL12 in endothelial cells. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138<sup>+</sup> IgA<sup>+</sup> PCs surrounding tumors. Abrogation of PCs decreased tumor burden, increased activated T cell infiltration, and reduced CD163<sup>+</sup>CD206<sup>+</sup> 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<sup>+</sup> PCs in the lungs.
Authors
- William Henry Hudson (ORCID: https://orcid.org/0000-0002-2513-1213)
- Yichao Shen (ORCID: https://orcid.org/0000-0002-5257-6808)
- Briana A. Burns (ORCID: https://orcid.org/0000-0002-6709-9581)
- Kelsey E. Mauk (ORCID: https://orcid.org/0000-0001-5985-4148)
- Cheng-Yen Chang (ORCID: https://orcid.org/0000-0002-3943-3044)
- William K. Decker (ORCID: https://orcid.org/0000-0003-0992-5838)
- Lizhen Song (ORCID: https://orcid.org/0000-0002-2448-7795)
- M J Hong (ORCID: https://orcid.org/0000-0002-2123-3554)
- Farrah Kheradmand (ORCID: https://orcid.org/0000-0001-5343-103X)
- Chad J. Creighton (ORCID: https://orcid.org/0000-0002-6090-703X)
- Dominique Armstrong
- Hyun‐Sung Lee (ORCID: https://orcid.org/0000-0001-8259-046X)
- David B. Corry (ORCID: https://orcid.org/0000-0001-9729-1016)
- Alexandre F. Carisey (ORCID: https://orcid.org/0000-0003-1326-2205)
- Xiang H.-F. Zhang (ORCID: https://orcid.org/0000-0002-5674-8670)
- Neil J. McKenna (ORCID: https://orcid.org/0000-0001-6689-0104)
- Sheetal Jammi
- B. Casal
- Linda K. Green (ORCID: https://orcid.org/0000-0003-2499-8816)
- Sung Wook Kang
Institutions
- Michael E. DeBakey VA Medical Center (US)
- Baylor College of Medicine (US)
- Texas Children's Hospital (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1126/sciadv.ads4227
- Citations
- 5
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.99