How emotions may impact tumor growth

Is it possible for us to "tell" the brain to boost the body's immune response against cancer tumors? Researchers believe that the answer is "yes," and that it can be done by manipulating the activity of the brain's reward system.

"The relationship between a person's emotional state and cancer has been demonstrated in the past, but mainly in relation to negative feelings such as stress and depression and without a physiological map of the action mechanism within the brain," says Prof. Asya Rolls.

Prof. Rolls is based at the Rappaport Faculty of Medicine at the Technion-Israel Institute of Technology in Haifa.

She and her colleagues have been puzzled by the notion that emotions, as processed by the brain, could somehow influence the turn that cancer tumors can take once lodged inside the body.

It is intuitive to consider that stress, anxiety, and depression could have a negative impact on the body's ability to fight disease. But could positive emotions, or a simulation of such emotions, reinforce the immune response?

"Several researchers," says Prof. Rolls, "including Prof. David Spiegel of the Stanford University School of Medicine [in California], have shown that an improvement in the patient's emotional state may affect the course of the disease." But, she also adds that "it was not clear how this happened."

So, Prof. Rolls and team decided to conduct a study to explore these mechanisms and learn more about how emotions in the brain can influence the way in which the immune system responds to cancer.

In a paper that has been published in the journal Nature Communications, the researchers report what they found through their recent study.

"We are now presenting a physiological model that can explain at least some of this effect," says Prof. Rolls.

An intricate communication system

Immunotherapy, which aims to boost the immune system's response against cancer cells, has been gaining ground in cancer research over the past few years.

"However," Prof. Rolls goes on, "the immune cells' involvement in cancerous processes is a double-edged sword, because certain components in these cells also happen to support tumor growth."

"They do so by blocking the immune response and creating an environment that is beneficial to growth," she explains.

But, as the researchers explain in the newly published paper, existing studies have suggested that activity in the brain's reward system can help regulate the way in which the immune system functions.

Based on these notions, Prof. Rolls and her colleagues conducted a preclinical study in which they experimented with manipulating the brain's reward system in mouse models of melanoma (skin cancer) and lung cancer.

Specifically, they "took aim" at the dopamine-releasing neurons found in the ventral tegmental area (VTA) of the brain, a key region of the reward system. The VTA communicates with the limbic system, a brain structure tasked with processing emotions, among other things.

And this, as the team found, interacts with the sympathetic nervous system, the network of neurons and nerves found partly in the central nervous system, and partly in the peripheral nervous system, which is known to regulate the fight-or-flight response.

This interaction, then, seemed to extend to the immune system. "By artificially activating [the VTA]," explains Prof. Rolls, "we can affect the nervous system and, in turn, the immune system."

Approach shrinks cancer tumors

Moreover, the researchers explain, once the immune system is activated in this way, it also appears to create a more resilient "memory" of the foreign agents to which it has been exposed, which allows it to respond more efficiently to those pathogens.

When they tested these effects in mouse models of melanoma and lung cancer, the team revealed that by stimulating the VTA, the immune system appeared to respond more effectively to the tumors.

The researchers saw that "after 14 days of repeated VTA activation," tumor size was reduced by 46.5 percent, on average, while tumor weight decreased by 52.4 percent, on average.

Though this study is preclinical, and it only looked at the effects of VTA stimulation in two types of cancer using mouse models, the researchers believe that their findings might influence the way in which healthcare practitioners view the role of mental state and emotional well-being in both the development and treatment of diseases such as cancer.

"Understanding the brain's influence on the immune system," explains study co-author Prof. Fahed Hakim, "and its ability to fight cancer will enable us to use this mechanism in medical treatments."

"Different people react differently, and we'll be able to take advantage of this tremendous potential for healing only if we gain a thorough understanding of the mechanisms."

Prof. Fahed Hakim

Prof. Rolls and colleagues have been researching the role of emotional states, and of the brain's reward system, in the modulation of immune responses for some time.

Below, Prof. Rolls explains what the mechanisms involved might be, drawing on a previous study that demonstrated how reward system activation can reinforce the immune system's response to harmful bacteria.