New Study Uncovers Link Between Mutated Cells, Autoimmune Conditions, and Cancer
A new study from Cold Spring Harbor Laboratory (CSHL), published in Nature, suggests a direct connection between the body's natural production of mutated cells and the onset of severe autoimmune conditions. The research indicates that the immune system possesses antibodies capable of both combating tumors and attacking brain tissue.
Unraveling Autoimmune Origins
Sam Kleeman, who led the study, proposed that some autoimmune conditions may originate from undiagnosed cancers. The team focused on anti-NMDA receptor encephalitis (ANRE), an autoimmune brain disease characterized by the immune system attacking NMDA receptors in the brain, leading to symptoms such as psychosis, insomnia, and seizures. Patients with ANRE are frequently found to have tumors that produce these same NMDA receptors outside the brain.
Sam Kleeman, who led the study, proposed that some autoimmune conditions may originate from undiagnosed cancers.
Experimental Evidence from Mouse Models
Using a mouse model of breast cancer, researchers tracked antibodies from their initial state to their evolution within a tumor into potent cancer-fighting molecules. Mice that developed strong antibody responses experienced spontaneous tumor shrinkage. However, when these same antibodies were introduced into the brains of healthy mice, they induced seizures and elevated body temperatures, similar to ANRE symptoms.
Mechanistic Insights into Antibody Action
CSHL Professor Hiro Furukawa used cryo-EM to observe that some antibodies activated NMDA receptors, while others inhibited them. This finding indicates that an immune response against a tumor can generate antibodies with contrasting effects on the brain.
Clinical Relevance in Breast Cancer
The team collaborated with Northwell Health and discovered that NMDA receptor proteins are commonly produced by tumors in patients with triple-negative breast cancer. Approximately 15% of these patients developed antibodies targeting NMDA receptors and tended to have improved clinical outcomes, suggesting an active immune response against the cancer.
Future Directions and Holistic Views
CSHL Associate Professor Tobias Janowitz stated that this knowledge could aid in designing antibody-based drugs to treat triple-negative breast cancer, emphasizing the importance of considering the body's holistic response to disease to solve long-standing biomedical mysteries.
This knowledge could aid in designing antibody-based drugs to treat triple-negative breast cancer, emphasizing the importance of considering the body's holistic response to disease to solve long-standing biomedical mysteries.