Newswise — By artificially activating the brain’s reward system, researchers at the Technion-Israel Institute of Technology have dramatically reduced the size of cancerous tumors in mice. The findings were published recently in the journal Nature Communications. The research was led by doctoral students Tamar Ben-Shaanan and Maya Schiller, under the supervision of Associate Professor Asya Rolls of the Rappaport Faculty of Medicine at the Technion and Assistant Prof. Fahed Hakim, medical director of the Scottish EMMS Hospital in Nazareth.

The immune system’s natural ability to destroy cancer cells has become increasingly clear in recent years. This realization has led to the growth of immunotherapy – an innovative medical approach based on the understanding that the immune system is able to fight cancer effectively if given the tools. In 2013, the editors of the journal Science called immunotherapy the most important breakthrough of the year. “However,” explains Prof. Rolls, “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.”

Prof.  Rolls has been studying the brain’s effect on the immune system for several years. In a study she and her colleagues published in 2016 in Nature Medicine, she showed how the immune system can be stimulated by manipulating the brain’s reward system – which operates in positive emotional states and in anticipation of the positive. “By artificially activating the region, we can affect the nervous system and, in turn, the immune system,” she said. In the same article, Prof. Rolls and her colleagues showed that artificial intervention sends messages to the sympathetic nervous system, which stimulates the immune system. The intervened-with immune system also created a stronger immune memory against the bacteria to which it had been exposed, which enables it to work more efficiently the next time it is exposed to the same bacteria.

Most immune system cells come from bone marrow – the spongy tissue found in bones. The brain communicates directly with bone marrow, and can affect its attributes. The main breakthrough in this study is the researchers’ success in harnessing the brain’s potential to boost the immune system in fighting cancer.

“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,” said Prof. Rolls. Several researchers, including Prof. David Spiegel of the Stanford University School of Medicine, have shown that an improvement in the patient’s emotional state may affect the course of the disease, but it was not clear how this happened. We are now presenting a physiological model that can explain at least some of this effect.”

“Understanding the brain’s influence on the immune system and its ability to fight cancer will enable us to use this mechanism in medical treatments,” said Prof. Hakim. “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.”

The authors caution that the study is preclinical, and note that they tested only two cancer models (melanoma and lung cancer) and only two development aspects – tumor volume and weight. However, they say this breakthrough will allow doctors to realize what physiological role the patients’ mental state may play in the development of malignant diseases. By artificially activating different parts of the brain, in the future it might be possible to encourage the immune system to block development of cancerous tumors more effectively.

About the researchers

Associate Professor Asya Rolls completed her bachelor’s and master’s degrees at the Technion’s Faculty of Biology, and after her doctorate at the Weizmann Institute of Science and post-doctorate at the Department of Psychiatry at Stanford University in California, she joined the Technion’s Rappaport Faculty of Medicine in 2012 as a faculty member. She was awarded the Adelis Brain Research Award, the Krill Prize, an European Research Council Grant, elected to the Israel Young Academy of Sciences and the FENS-kavli network of excellence, and recognized as one of 40 international researchers by the Howard Hughes Medical Institute (HHMI). She is also a member of the Technion Integrated Cancer Center (TICC).

Clinical Prof. Fahed Hakim was recently appointed Medical Director of the Scottish EMSS Hospital in Nazareth and continues to serve as the Senior Physician at the Pediatric Lung Institute at the Rambam Health Care Campus in Haifa. Prof. Hakim is an expert in pediatrics, pediatric pulmonology, and sleep disorders. He is an active member of the respective international associations for the study of lung disease, sleep, and brain research. After completing a postdoctoral fellowship at the Department of Sleep Research at the University of Chicago in Illinois in 2013, he joined the Technion’s Rappaport Faculty of Medicine as a faculty member.

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1. Assoc. Prof. Asya Rolls

2. Asst. Prof. Fahed Hakim

3. Doctoral students Tamar Ben-Shaanan (left) and Maya Schiller

4. Dr. Hilla Azulay-Debby

5. Group photo (L-R): Dr. Azulay-Debby, Prof. Rolls, Prof. Hakim and Maya Schiller

6. Image b: Image of the reward system (VTA). Experimental mice were injected with a special compound known as a DREADD, that allows researchers to manipulate the brain and activate the reward system. The red is the DREADD expression limited to the reward system; the green is the dopaminergic neurons activated by manipulating the reward system.

7. Image d: The upper row is tumors that developed in the control group of mice; the bottom row is tumors from mice that underwent brain manipulation. (Photo Credit: Rami Shlush, Technion Spokesperson’s Office)

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Journal Link: Nature Communications, Jul 13-2016