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.

中文翻译：

---

大脑奖励系统调节抗肿瘤免疫。

调节免疫力是癌症治疗的主要靶点。在这里，我们表明抗肿瘤免疫反应可以受到大脑奖励系统的调节，这是情绪过程中的关键回路。使用化学遗传学 （DREADD） 激活荷瘤小鼠 （Lewis 肺癌 （LLC） 和 B16 黑色素瘤）的奖励系统，导致肿瘤重量减轻。这种作用是通过交感神经系统 （SNS） 介导的，表现为对主要免疫部位（骨髓）的去甲肾上腺素能输入减弱。在骨髓中发育的髓源性抑制细胞 （MDSC） 在奖励系统激活后免疫抑制作用降低。通过耗竭或过继转移 MDSC，我们证明了这些细胞对于介导奖励系统对肿瘤生长的影响既必要又充足。鉴于奖励系统在积极情绪中的核心作用，这些发现引入了一种生理机制，患者的心理状态可以影响抗肿瘤免疫和癌症进展。