The Biohackers Within

“Cancer cells hijack nerves, communicate with the brain, and suppress the immune system. A potential avenue for new therapies?

 

In 2024, 230,392 people in Germany officially died of cancer; only cardiovascular diseases claim more lives.

 

For a long time, cancer was viewed as a largely isolated disease process. Malignant cells proliferate autonomously, form metastases, and become a life-threatening danger. However, this perception has shifted in recent years. Cancer cells do not exist in isolation; rather, they operate within a finely balanced biological network comprising immune cells, connective tissue, blood vessels—and nerves.

 

It has long been known that many solid tumors are permeated by nerve fibers. Signals from these fibers can dampen the activity of the body's own defense cells, allowing the tumor to continue growing. Until now, however, the mechanisms driving this interaction remained unclear. A US research study published in *Nature* sheds light on the matter. It reveals that tumors are apparently capable of functionally "hijacking" nerve cells in their immediate vicinity and establishing a direct communication link to the brain. Cancer thus operates in a far more complex manner than previously assumed, utilizing neuronal networks to ensure its survival even during treatment.

 

In their study, the research team from the University of Pennsylvania focused on lung adenocarcinoma, a common form of lung cancer. Through experiments on mice in which the disease was genetically induced, the researchers first demonstrated that these carcinomas are densely permeated by nerve fibers from the vagus nerve. In the human body, the vagus nerve acts as a data highway connecting internal organs to the brain. It continuously transmits information regarding the functional status of the heart, lungs, liver, spleen, and gastrointestinal tract to the brain. There it processes information from the organs and triggers reactions as needed.

 

A striking feature was the high density of vagal fibers within the tumor tissue. Cell culture experiments further revealed that the tumors can actively attract these nerve fibers. They produced increased levels of neurotrophic factors, which promote nerve fiber growth. Moreover, RNA sequencing of the nerve cells in question showed that they alter their pattern of genetic activity under the tumor's influence.

 

Genes relevant to signal processing, immune response, and nerve growth were significantly upregulated.

 

This suggests that tumors can reprogram nerve cells to support cancer growth.

 

But how exactly do these neuronal connections influence the cancer? Sensory nerves transmit information from the periphery to the brain. When vagus nerve fibers are activated, they send signals to a control center in the brainstem, among other locations. From there, the sympathetic nervous system—the part of the autonomic nervous system that regulates organ function during stress or emergencies—is activated via the messenger substance noradrenaline. The lung carcinoma under study appears to utilize this very signaling pathway: signals originating from the nerve fibers within the tumor trigger a chain of events that, via the brainstem, elicits a sympathetic response in the lungs—thereby causing changes in the tumor's immediate environment.

 

However, the noradrenaline released during this stress response does not appear to have a direct effect on the cancer cells themselves. Instead, the signal targets immune cells. So-called alveolar macrophages reside in the lung's alveoli and normally constitute the lung's first line of defense; for instance, they clear away inhaled dust particles, allergens, or pathogens. Yet, under the influence of noradrenaline, they alter their behavior. Rather than supporting a defensive response, they inhibit the activity of certain T cells— the immune cells capable of recognizing and specifically destroying tumor cells. Tumor growth is thus indirectly promoted. "These new findings regarding the interaction between the brain, nerves, the immune system, and lung cancer demonstrate that cancer is indeed a systemic disease involving many—if not all—areas of the human body," says Frank Winkler of the Department of Neurology at Heidelberg University Hospital and Head of Experimental Neuro-Oncology at the German Cancer Research Center (DKFZ). His research has contributed significantly to understanding the close interplay between nerves and tumors. With regard to the US study, he emphasizes: "The brain itself is part of a vast feedback loop. It can reprogram our immune system so that it is no longer able to act against cancer."

 

The rapidly growing importance of this field of research was also evident at the German Cancer Congress in Berlin, where an entire session was dedicated to cancer neuroscience. There, Ghazaleh Tabatabai of the University Hospital Tübingen emphasized that the interaction between tumors and the nervous system represents a "fundamental mechanism." This potentially offers numerous therapeutic targets.

 

In a series of experiments, scientists from the USA intervened at specific points along the signaling pathway—targeting both vagal nerve cells in the lungs and the relevant neurons in the brainstem. They also blocked the effects of the signaling molecule noradrenaline within the tumor tissue by disabling its primary receptor. Consistently similar effects were observed: lung tumors grew significantly more slowly, and the activity of T-cells directed against the tumor increased.

 

It remains unclear whether these observations can be translated to humans. "These are, in fact, experimental models that have been studied very robustly. However, evidence that this mechanism is also active in humans is still lacking," said Winkler. While the nerve-tumor connection has been observed in cancer patients, the human immune system is more complex, human tumors are genetically more heterogeneous, and neuronal circuitry differs between mice and humans. It is also unclear whether this is a lung-specific signaling pathway to the immune system or if other types of tumors—such as gastric or pancreatic cancer—utilize similar vagal pathways to inhibit immune cells.

 

To translate these findings into therapeutic applications, Christian Reinhardt—Director of the Department of Hematology and Stem Cell Transplantation at the University Hospital Essen—identifies a clear next step: "We need technologies that allow us to precisely map the neuronal landscape of a tumor." Reinhardt supervised a study that described the connection between nerve cells and small-cell lung cancer. Given the heterogeneity of tumors, biomarker research—specifically, identifying which patients might actually benefit from a given therapy—is also crucial.

 

Overall, Reinhardt is optimistic: "We already have a wide range of substances that interact with the nervous system. This facilitates and accelerates the path to clinical application." Many of these drugs have been in use for decades, for instance, to treat pain or anxiety. He considers it quite possible that an additional therapy could enhance the efficacy of existing chemotherapy and immunotherapy regimens. Nevertheless, he urges caution. Interventions affecting the nervous system have broad effects; they can also influence attention, mood, or mental alertness. "Our goal must be to strike a balance between controlling the tumor and preserving autonomy and dignity."

 

Undoubtedly, deciphering the connectivity of solid tumors opens up a new dimension in tumor biology. For the first time, it is becoming clear that neural circuits play an active role in the disease process. The better these networks are understood, the more targeted future interventions may become.” [1]

 

 

1. Die Biohacker im Leib. Frankfurter Allgemeine Zeitung; Frankfurt. 18 Mar 2026: N1. Von Charlotte Braatz