Lung cancer tricks brain to trick immune system Scientific American

Research shows that lung cancer cells in mice communicate with the brain and send signals that turn off the body's immune response.

For years, scientists thought of cancer as a localized lesion where cells refuse to divide, but new research shows that tumors in certain organs actively communicate with the brain, tricking the brain into protecting itself.

Scientists have long known that some tumors grow into nerves and that tumors with more nerves have a worse prognosis.But they didn't know exactly why.“Before our study, most of this local interaction between the [end of] the nerve and the tumor was concentrated,” says Chengcheng Jin, assistant professor of cancer biology at the University of Pennsylvania and co-author of the study published today in the journal Nature.

Jin and his colleagues discovered that lung cancer tumors in mice can use these nerve endings to communicate outside their immediate vicinity and send signals to the brain through a complex immune circuit.They also confirmed that this circuit exists in humans.

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Creating this circuit begins with a process called innervation, where the lung tumor inserts itself into the vagal nerve - the internal information pathway that connects vital organs to the brain.In this way, Jin's team discovered a special group of neurons that communicate directly with the central nervous system."Our study shows that tumors bypass the current path to self-repair," explained Rui Chang, professor of neuroscience at Yale School of Medicine and study author.

When the stomach grows, it uses vagus neurons to send signals to the nucleus accumbens, an area of ​​the brain that supports functions such as blood pressure, heart rate, or digestion.The code sent by the drive using this system is similar to the malicious code used by the attacker.

Instead of recognizing the tumor as an invader that needs to be destroyed, the brain processes the signal and activates the sympathetic nervous system, which is essentially the controller of the fight-or-flight response.This sympathetic surge is triggered by the release of norepinephrine, which has devastating consequences in cancer.

Norepinephrine is released directly into the immediate vicinity of the tumor, where it binds to macrophages, cells in the first line of the immune system that recognize, eat and destroy threats.Macrophages are covered with docking stations called β2-adrenergic receptors, which normally tell the cells when to be aggressive and when to "cool down," preventing the immune system from destroying healthy cells.When norepinephrine released from brain-controlled nerves binds to these receptors, it effectively reprograms the macrophages to switch sides.

In this suppressed state, they begin to release chemical signals that act as a "do not disturb" signal to the rest of the immune system.This neutralizes one of the body's most effective weapons: T cells, specialized killers that physically kill cancer cells.Since the brain has ordered the macrophages to form an immunosuppressive shield, the T cells lose their energy, stop proliferating and fail to recognize the cancer as a threat.live

"The authors have depicted an entire bidirectional tumor-neuropathway that promotes tumor growth that has great relevance to human health," says Catherine Dulac, professor of molecular and cellular biology at Harvard University, who was not involved in the study.

Jin and his team also looked for ways to stop tumors from talking to the brain.By mapping this line from the lungs to the brain and back again, the researchers identified several new places where they could "cut the wire."Studies have shown that blocking any part of the brain tumor circuit re-triggers the immune system.

"Obviously, the prospects for applications in cancer treatment are very promising," Dulac said.However, Jin and Chang say we are still a long way from translating our findings into treatment strategies.

"We're talking about transitioning from a mouse model to a human. I think there's still a long way to go," Chang says.