Researchers at Baylor College of Medicine and collaborating institutions have uncovered a mechanism by which tumors evade the body's immune response, as detailed in a recent study published in Science Advances. The study highlights the role of the protein MAGE-4 and the loss of the tumor suppressor gene Pten in accelerating tumor progression to metastasis in non-small cell lung cancer.
Dr. Farrah Kheradmand, corresponding author and professor at Baylor, explained, “It’s known that patients with lung cancers that express MAGE-4 have an unfavorable prognosis, but whether or how this protein helps cancer grow was not well understood.” The research involved developing a mouse model expressing MAGE-4 to explore its effects on cancer growth.
Unexpectedly, initial attempts showed no cancer development until further analysis by Dr. Chad Creighton revealed that tumors expressing MAGE-4 also lacked PTEN. This discovery led to creating a new mouse model where both conditions were present, resulting in aggressive and metastatic tumor growth.
“We were excited about this finding because it showed that MAGE-4 was not only an indicator of severity and poor prognosis but also pushed cancer forward in combination with the loss of a tumor suppressor gene,” Kheradmand noted.
The team discovered that these tumors attracted plasma cells producing IgA antibodies along with IL-10 and TGF-beta compounds, which suppress immune responses. Lung endothelial cells produced CXCL12, drawing more plasma cells into the tumor microenvironment while excluding immune T cells.
“Our findings were corroborated in human samples,” Kheradmand stated. Dr. Linda Green identified these plasma cells surrounding human non-small cell lung cancer tumors as significant contributors to disease progression.
The study suggests potential therapeutic strategies for removing plasma cells from MAGE-A4 expressing tumors to enhance T cell infiltration and improve antitumor immunity. Future steps could involve clinical trials to test this approach's effectiveness against solid tumors.
Contributors to this research include Dominique Armstrong, Cheng-Yen Chang, Monica J. Hong, Yichao Shen, William Hudson, among others from Baylor College of Medicine and associated institutions.
For complete funding details, refer to the publication.
