Consider two seemingly unrelated medical puzzles. First: Every day, our bodies generate hundreds of billions of new cells, many of which mutate. If cancer arises from cell mutations, why don’t we all get the disease all the time?Second, severe autoimmune diseases such as lupus and multiple sclerosis often develop without warning. No one knows what triggers them. A new study from Cold Spring Harbor Laboratory (CSHL) shows that naturesuggesting that the two puzzles may be directly connected. This research has revealed that our immune systems are pre-equipped with antibodies that fight tumors and attack the brain.
”Patients with autoimmune diseases often have symptoms that appear out of nowhere.” said Sam Kleeman, a recent graduate of the CSHL doctoral program who led the study.It could be from a cancer you didn’t know you had.”
Kleeman’s team focused on anti-NMDA receptor encephalitis (ANRE), a debilitating autoimmune brain disease popularized by Susannah Cahalan. new york times bestseller brain on fire. In ANRE, the immune system attacks proteins in the brain called NMDA receptors, causing psychosis, insomnia, and seizures. It turns out that many patients with this condition have tumors outside their brains that produce the same NMDA receptors.
Using mouse models of breast cancer, the researchers tracked antibodies as they evolved from precursors present at birth into potent cancer-killing molecules within tumors. Mice with the strongest antibody responses were observed to have spontaneous tumor shrinkage. However, when the same antibody was injected into the brains of healthy mice, it triggered seizures and increased body temperature, similar to what ANRE patients experience.
An important advance was made by Professor Hiroshi Furukawa of CSHL, an expert in molecular neuroscience. Using a method called cryo-EM, he noticed that some antibodies activated NMDA receptors, while others inhibited them.
This means that the same immune response against a tumor can produce antibodies that have exactly the opposite effect on the brain. Understanding which antibodies are harmful and which are protective could ultimately help develop treatments that prevent damage to the nervous system while preserving the immune system’s ability to fight cancer. ”
Hiroshi Furukawa CSHL Professor
With this goal in mind, the team turned its attention to the clinic. Researchers, in collaboration with Northwell Health, discovered that the NMDA receptor protein is commonly produced by tumors in triple-negative breast cancer patients, which are known to be resistant to hormone therapy and other common treatments. Approximately 15% of these patients developed antibodies targeting the NMDA receptor. Notably, these patients tend to have better clinical outcomes, suggesting that the immune system is actively fighting the cancer.
“With this knowledge, we can begin the careful design of antibody-based drugs that can be used in the future to treat patients with triple-negative breast cancer.” said CSHL Associate Professor Tobias Janowitz, who supervised the research with Furukawa.Our study shows that while cancer remains highly enigmatic, considering the whole body’s response to the disease may help solve biomedical mysteries that have eluded scientists for decades.”
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Cold Spring Harbor Laboratory
Reference magazines:
Thor Kleeman, others. (2026). Ectopic NMDAR expression in cancer reveals germline-encoded autoimmunity. Nature. DOI: 10.1038/s41586-026-10278-0. https://www.nature.com/articles/s41586-026-10278-0
