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Israeli Researchers have shrunk cancerous tumors in mice by manipulating the brain’s reward system

Researchers at the Technion have used successfully immunotherapy: the intervention caused the nervous system to stimulate the immune system.

Group photo (L-R) Dr. Azulay-Debby, Prof. Rolls, Prof. Hakim and Maya Schiller Credit Rami Shlush, Technion Spokesperson’s office

A breakthrough preclinical study at the Technion Israel successfully shrunk melanoma and lung cancer tumors in mice. The researchers used the brain’s reward system to lead to a dramatic reduction in the tumor volume and weight.

The conclusion of a study published in the journal Nature Communications

The immune system’s natural ability to destroy cancer cells has become increasingly clear in recent years. This 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 journal Science called immunotherapy ‘the most important breakthrough of the year’. “However,” explains Prof. Asya Rolls of the Technion, “the immune cells’ involvement in cancerous processes is a double-edged sword because certain components in these cells support tumor growth. This is done by blocking the immune response and creating an environment that is beneficial to growth.”

Most immune cells come from the 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 immune system and preventing the cancerous tumor from taking over. The result is a dramatic contraction of the cancerous tumor in response to the activation of the brain 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,” Prof. Rolls said.

The upper row is tumors that developed in the control group of mice; the bottom row is tumors from mice that underwent brain manipulation.

Several researchers, for example, Prof. David Spiegel of the Stanford University School of Medicine showed 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 part of this effect,” She said.

Prof. Rolls previous study published in 2016 in Nature Medicine, 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.

She says, “By artificially activating the region, we can affect the nervous system and, in turn, the immune system.”

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. Moreover, as a result of the intervention, the immune system created a stronger immune memory against the bacteria to which it had been exposed, therefore it will work more efficiently the next time it is exposed to the same bacteria.

The authors pointed out that this breakthrough results will allow doctors to realize the 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.

“I want to emphasize what our findings do not say,” Prof. Rolls said. “They do not say that it is applicable for all types of cancer and most importantly that it is not applicable to humans at this point. It is a robust artificial type of manipulation, designed to determine the system’s potential. In real-life situations, it most probably works differently, especially because other systems are also involved. For example, stress may counteract these reward system effects. I think it’s crucial for people to know that it’s not that one can just think positively and get better. People are very different in their reactions, and until we fully understand how this works, it merely offer a potential.

The research was led by doctoral students Tamar Ben-Shaanan and Maya Schiller, under the supervision of Assoc. Prof. Asya Rolls of the Technion Rappaport Faculty of Medicine and Technion Asst. Prof. Fahed Hakim, Medical Director of the Scottish EMMS Hospital in Nazareth.

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