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.