Stimulation of brain’s reward system reduces cancer tumours

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.

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 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 support tumour growth. This is done 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 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.

She said, “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.

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 tumour from taking over. The result is a dramatic contraction of the cancerous tumour 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.

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.”

According to Prof. Hakim, “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. 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 pointed out that the study is preclinical and that they tested only two cancer models (melanoma and lung cancer) and only two developmental aspects – tumour volume and weight.

However, this breakthrough will allow doctors to realise 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 tumours more effectively.

“I want to emphasise 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 offers a potential.”