Modulation of anti-tumor immunity by the brain’s reward system

Tamar L Ben-Shaanan, Maya Schiller, Hilla Azulay-Debby, Ben Korin, Nadia Boshnak, Tamar Koren, Maria Krot, Jivan Shakya, Michal A. Rahat, Fahed Hakim () and Asya Rolls ()
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Tamar L Ben-Shaanan: Technion - Israel Institute of Technology
Maya Schiller: Technion - Israel Institute of Technology
Hilla Azulay-Debby: Technion - Israel Institute of Technology
Ben Korin: Technion - Israel Institute of Technology
Nadia Boshnak: Technion - Israel Institute of Technology
Tamar Koren: Technion - Israel Institute of Technology
Maria Krot: Technion - Israel Institute of Technology
Jivan Shakya: Technion - Israel Institute of Technology
Michal A. Rahat: Technion - Israel Institute of Technology
Fahed Hakim: Technion - Israel Institute of Technology
Asya Rolls: Technion - Israel Institute of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Regulating immunity is a leading target for cancer therapy. Here, we show that the anti-tumor immune response can be modulated by the brain’s reward system, a key circuitry in emotional processes. Activation of the reward system in tumor-bearing mice (Lewis lung carcinoma (LLC) and B16 melanoma) using chemogenetics (DREADDs), resulted in reduced tumor weight. This effect was mediated via the sympathetic nervous system (SNS), manifested by an attenuated noradrenergic input to a major immunological site, the bone marrow. Myeloid derived suppressor cells (MDSCs), which develop in the bone marrow, became less immunosuppressive following reward system activation. By depleting or adoptively transferring the MDSCs, we demonstrated that these cells are both necessary and sufficient to mediate reward system effects on tumor growth. Given the central role of the reward system in positive emotions, these findings introduce a physiological mechanism whereby the patient’s psychological state can impact anti-tumor immunity and cancer progression.

Date: 2018
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DOI: 10.1038/s41467-018-05283-5

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