DA-DRD5 signaling promotes B cells antitumor immunity by activating JAK-STAT pathway

Neuronal signals have emerged as pivotal regulators of B cells that regulate antitumor immunity and tumor progression. The functional relevance and mechanistic basis of effects of the neurotransmitter dopamine (DA) on tumor immunity remain unclear. Here, we found that the abundance of DA was positively correlated with circulating B cell numbers and potently activated B cell responses in a DRD5-receptor-dependent manner. The deficiency of DRD5 signaling reduced B cell responses and promoted tumor progression. Transcriptome analysis revealed that dopamine activated JAK1-STAT1 signaling. DRD5 agonist boosted antitumor immunity and anti-programmed cell death protein 1(anti-PD-1) immunotherapy. Our results demonstrate that dopamine signaling which suppresses tumor progression and suggest DRD5 as a potential target for cancer immunotherapy.

神经元信号已被证实为调控B细胞的关键调控因子，而B细胞参与抗肿瘤免疫与肿瘤进展的调控。神经递质多巴胺（dopamine，DA）对肿瘤免疫产生影响的功能关联性与分子机制，目前仍未明确。本研究发现，多巴胺的丰度与循环B细胞数量呈正相关，并可通过依赖多巴胺D5受体（DRD5）的方式强效激活B细胞应答。DRD5信号通路缺陷会削弱B细胞应答，并促进肿瘤进展。转录组分析结果显示，多巴胺可激活JAK1-STAT1信号通路。DRD5激动剂可增强抗肿瘤免疫与抗程序性死亡蛋白1（anti-PD-1）免疫治疗的疗效。本研究结果证实，多巴胺信号通路可抑制肿瘤进展，并提示DRD5可作为癌症免疫治疗的潜在靶点。