Cancer takes a devastating toll on the body—but the psychological burden can be just as profound. Many patients, even those with a long history of resilience and optimism, experience notable emotional downturns. New research points to a biological explanation: the lack of motivation and emotional withdrawal may be a direct result of cancer cachexia, a wasting syndrome that is commonly observed in advanced cancer patients.
In a Science study titled, “A neuroimmune circuit mediates cancer cachexia-associated apathy,” researchers at Cold Spring Harbor Laboratory (CSHL) and Washington University School of Medicine in St. Louis (WashU Medicine), identified a brain-immune system circuit responsible for the motivational decline in cachexia. Inflammation disrupts brain signaling and suppresses dopamine, which is responsible for drive and reward.
“Cachexia is a debilitating wasting syndrome that affects most advanced cancer patients, characterized by profound involuntary weight loss, muscle, and fat depletion, and disrupted energy balance,” wrote the authors. Previous research linked cachexia to chronic inflammation and changes in metabolism, but until now, the neural mechanisms behind behavioral symptoms like apathy remained unclear.
To explore the connection between the apathy symptoms and immune responses, the team studied mouse models of cancer cachexia and screened for changes in immune system activity and neurotransmitter levels. They found that a region of the brainstem as as a sensor for inflammation signals, specifically interleukin-6 (IL-6). Elevation in IL-6 neurons transmits a signal to the nucleus accumbens, suppressing the release of dopamine and reducing the motivation of mice to exert themselves to complete activities.
“We discovered a full brain circuit that senses inflammation in the bloodstream and sends signals that reduce motivation,” said Adam Kepecs, PhD, professor of neuroscience at WashU Medicine.
The researchers went a step further to test whether manipulating this circuit could reverse the symptoms. Reducing IL-6 signaling in the brainstem restored motivation in mice, making them less sensitive to the effort required to seek out food. Similarly, pharmacologically boosting dopamine levels yielded the same behavioral improvements. Although motivation was restored, cancer and weight loss symptoms continued to progress, indicating that cachexia-derived apathy can be treated separately from cancer.
“We’ve uncovered a direct brain mechanism through which inflammation drives apathy in cancer, and we were able to restore normal motivation in mice with cachexia, despite ongoing inflammation as cancer progressed,” said Kepecs. “Apathy isn’t just an emotional or psychological reaction to cachexia—it’s built into the biology of the disease.”
The findings open a promising new avenue for clinical intervention. Antibody-based therapies that target IL-6 already exist and are in use for other inflammatory conditions. These could potentially be repurposed to ease motivational deficits in cancer patients with cachexia, improving their mental state, appetite, and response to treatment.
“What’s remarkable is that motivation was restored even in late-stage disease,” said Marco Pignatelli, MD, an assistant professor of psychiatry at WashU Medicine. “It suggests we may be able to improve quality of life by targeting the brain circuit.”
The researchers emphasize that while more work is needed to translate these findings to human patients, the implications are broad. Beyond cancer, similar brain-immune pathways may underlie fatigue and emotional decline in other chronic illnesses characterized by systemic inflammation.
“Our goals are to make patients feel better and to treat the cancer better,” said Tobias Janowitz, MD, PhD, associate professor at CSHL. “A better patient will be able to better tolerate and benefit from anti-cancer treatments.”
Ultimately, the authors hope their work will lead to new tools that improve both the longevity and quality of life of people living with cancer.
“This gives us a new way to understand apathy in advanced cancer,” said Kepecs. “It’s not just a byproduct of physical decline, but a direct response to inflammation in the brain. That means we can potentially target the underlying biology to improve motivation and quality of life—even when the cancer itself is no longer treatable.”
The post Apathy in Cancer Patients Linked to Brain-Immune Circuit appeared first on GEN - Genetic Engineering and Biotechnology News.
In a Science study titled, “A neuroimmune circuit mediates cancer cachexia-associated apathy,” researchers at Cold Spring Harbor Laboratory (CSHL) and Washington University School of Medicine in St. Louis (WashU Medicine), identified a brain-immune system circuit responsible for the motivational decline in cachexia. Inflammation disrupts brain signaling and suppresses dopamine, which is responsible for drive and reward.
“Cachexia is a debilitating wasting syndrome that affects most advanced cancer patients, characterized by profound involuntary weight loss, muscle, and fat depletion, and disrupted energy balance,” wrote the authors. Previous research linked cachexia to chronic inflammation and changes in metabolism, but until now, the neural mechanisms behind behavioral symptoms like apathy remained unclear.
To explore the connection between the apathy symptoms and immune responses, the team studied mouse models of cancer cachexia and screened for changes in immune system activity and neurotransmitter levels. They found that a region of the brainstem as as a sensor for inflammation signals, specifically interleukin-6 (IL-6). Elevation in IL-6 neurons transmits a signal to the nucleus accumbens, suppressing the release of dopamine and reducing the motivation of mice to exert themselves to complete activities.
“We discovered a full brain circuit that senses inflammation in the bloodstream and sends signals that reduce motivation,” said Adam Kepecs, PhD, professor of neuroscience at WashU Medicine.
The researchers went a step further to test whether manipulating this circuit could reverse the symptoms. Reducing IL-6 signaling in the brainstem restored motivation in mice, making them less sensitive to the effort required to seek out food. Similarly, pharmacologically boosting dopamine levels yielded the same behavioral improvements. Although motivation was restored, cancer and weight loss symptoms continued to progress, indicating that cachexia-derived apathy can be treated separately from cancer.
“We’ve uncovered a direct brain mechanism through which inflammation drives apathy in cancer, and we were able to restore normal motivation in mice with cachexia, despite ongoing inflammation as cancer progressed,” said Kepecs. “Apathy isn’t just an emotional or psychological reaction to cachexia—it’s built into the biology of the disease.”
The findings open a promising new avenue for clinical intervention. Antibody-based therapies that target IL-6 already exist and are in use for other inflammatory conditions. These could potentially be repurposed to ease motivational deficits in cancer patients with cachexia, improving their mental state, appetite, and response to treatment.
“What’s remarkable is that motivation was restored even in late-stage disease,” said Marco Pignatelli, MD, an assistant professor of psychiatry at WashU Medicine. “It suggests we may be able to improve quality of life by targeting the brain circuit.”
The researchers emphasize that while more work is needed to translate these findings to human patients, the implications are broad. Beyond cancer, similar brain-immune pathways may underlie fatigue and emotional decline in other chronic illnesses characterized by systemic inflammation.
“Our goals are to make patients feel better and to treat the cancer better,” said Tobias Janowitz, MD, PhD, associate professor at CSHL. “A better patient will be able to better tolerate and benefit from anti-cancer treatments.”
Ultimately, the authors hope their work will lead to new tools that improve both the longevity and quality of life of people living with cancer.
“This gives us a new way to understand apathy in advanced cancer,” said Kepecs. “It’s not just a byproduct of physical decline, but a direct response to inflammation in the brain. That means we can potentially target the underlying biology to improve motivation and quality of life—even when the cancer itself is no longer treatable.”
The post Apathy in Cancer Patients Linked to Brain-Immune Circuit appeared first on GEN - Genetic Engineering and Biotechnology News.