2. Academic Validation
  3. DA-DRD5 signaling reprograms B cells to promote CD8+ T cell-mediated antitumor immunity

DA-DRD5 signaling reprograms B cells to promote CD8+ T cell-mediated antitumor immunity

  • Cell Rep. 2025 Mar 25;44(3):115364. doi: 10.1016/j.celrep.2025.115364.
Yuqing Wu 1,  Lei Zhu 2,  Sheng Li 3,  Lu Liu 4,  Yaman Wang 1,  Yongbing Yang 5,  Yuan Mu 1,  Qiuying Zhu 6,  Yuying Jiang 4,  Chunyan Wu 7,  Peiwen Xi 8,  Chunmei Ma 4,  Lijun Liang 9,  Min Gao 10,  Yingchao Hu 11,  Qiang Ding 12,  Shiyang Pan 13
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Branch of National Clinical Research Center for Laboratory Medicine, Nanjing 210029, China.
  • 2 Jiangsu Breast Disease Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210036, China; Department of Breast Surgery, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing 210004, China.
  • 3 Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
  • 4 Department of Immunology, Nanjing Medical University, Nanjing 211166, China.
  • 5 Department of Medical Laboratory, Affiliated Children's Hospital of Jiangnan University, Wuxi 214000, China.
  • 6 The First Clinical School of Nanjing Medical University, Nanjing 210029, China.
  • 7 Department of Pathology, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing 210004, China.
  • 8 Department of Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 9 Department of Thoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
  • 10 Department of Nephrology, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200336, China.
  • 11 Department of Immunology, Nanjing Medical University, Nanjing 211166, China. Electronic address: yingchao@njmu.edu.cn.
  • 12 Jiangsu Breast Disease Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210036, China. Electronic address: dingqiang@njmu.edu.cn.
  • 13 Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Branch of National Clinical Research Center for Laboratory Medicine, Nanjing 210029, China. Electronic address: sypan@njmu.edu.cn.
PMID: 40023842 DOI: 10.1016/j.celrep.2025.115364
Abstract

Neuronal signals have emerged as pivotal regulators of B cells that regulate antitumor immunity and tumor progression. However, the functional relevance and mechanistic basis of the effects of the neurotransmitter dopamine (DA) on tumor immunity remain elusive. Here, we discovered that plasma DA levels are positively correlated with circulating B cell numbers and potently activate B cell responses in a manner dependent on the DRD5 receptor. Notably, DRD5 signaling enhanced the Janus kinase 1 (JAK1)-STAT1 signaling in B cell responses, which enhanced B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion and cytotoxicity in tumor-specific effector of T cells. Our findings demonstrate that DA signaling suppresses tumor progression and highlight DRD5 as a promising target for Cancer Immunotherapy.

Keywords

B cell; CP: Cancer; CP: Immunology; antitumor immunity; dopamine; dopamine receptor 5.

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