Potential Roles of Peripheral Dopamine in Tumor Immunity

Zhang, Xiang; Liu, Qiaofei; Liao, Quan; Zhao, Yupei

doi:10.7150/jca.20850

Cited by 41 publications

(24 citation statements)

References 99 publications

(113 reference statements)

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“…Therefore, immune responses controlled by DA mediate the effects of this neurotransmitter in cancer progression. Immune cells, including B lymphocytes, NK cells, monocytes, macrophages, dendritic cells, neutrophils, effector and regulatory T cells express dopamine receptors, 245 which are either coupled to Gs (D1R and D5R) or Gi (D2R, D3R, and D4R). Dopamine is produced not only by the brain, but also by peripheral organs including the digestive tract, spleen, and pancreas.…”

Section: Classical Central Nervous System Neurotransmitters (Dopaminementioning

confidence: 99%

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

145

112

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Normal cells are hijacked by cancer cells forming together heterogeneous tumor masses immersed in aberrant communication circuits that facilitate tumor growth and dissemination. Besides the well characterized angiogenic effect of some tumor-derived factors; others, such as BDNF, recruit peripheral nerves and leukocytes. The neurogenic switch, activated by tumor-derived neurotrophins and extracellular vesicles, attracts adjacent peripheral fibers (autonomic/sensorial) and neural progenitor cells. Strikingly, tumor-associated nerve fibers can guide cancer cell dissemination. Moreover, IL-1β, CCL2, PGE 2 , among other chemotactic factors, attract natural immunosuppressive cells, including T regulatory (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, to the tumor microenvironment. These leukocytes further exacerbate the aberrant communication circuit releasing factors with neurogenic effect. Furthermore, cancer cells directly evade immune surveillance and the antitumoral actions of natural killer cells by activating immunosuppressive mechanisms elicited by heterophilic complexes, joining cancer and immune cells, formed by PD-L1/PD1 and CD80/CTLA-4 plasma membrane proteins. Altogether, nervous and immune cells, together with fibroblasts, endothelial, and bone-marrow-derived cells, promote tumor growth and enhance the metastatic properties of cancer cells. Inspired by the demonstrated, but restricted, power of anti-angiogenic and immune cell-based therapies, preclinical studies are focusing on strategies aimed to inhibit tumor-induced neurogenesis. Here we discuss the potential of anti-neurogenesis and, considering the interplay between nervous and immune systems, we also focus on anti-immunosuppression-based therapies. Small molecules, antibodies and immune cells are being considered as therapeutic agents, aimed to prevent cancer cell communication with neurons and leukocytes, targeting chemotactic and neurotransmitter signaling pathways linked to perineural invasion and metastasis.

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Section: Classical Central Nervous System Neurotransmitters (Dopaminementioning

confidence: 99%

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

145

112

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“…DCs, a specialized antigen-presenting cells, can capture and processing of tumor-derived antigens, which play a crucial role in anti-immune response 101. Tumor-derived antigens are cross-presented to CD8+T cells by dendritic cells, inducing differentiation of CD8+T cells into cytotoxic T lymphocytes (CTLs).…”

Section: Dopamine Receptor and Tumor Immunitymentioning

confidence: 99%

The Prospective Value of Dopamine Receptors on Bio-Behavior of Tumor

Wang¹,

Wang²,

Luo³

et al. 2019

J. Cancer

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Dopamine receptors are belong to the family of G protein-coupled receptor. There are five types of dopamine receptor (DR), including DRD1, DRD2, DRD3, DRD4, and DRD5, which are divided into two major groups: the D1-like receptors (DRD1 and DRD5), and the D2-like receptors (DRD2, DRD3, and DRD4). Dopamine receptors are involved in all of the physiological functions of dopamine, including the autonomic movement, emotion, hormonal regulation, dopamine-induced immune effects, and tumor behavior, and so on. Increasing evidence shows that dopamine receptors are associated with the regulation of tumor behavior, such as tumor cell death, proliferation, invasion, and migration. Recently, some studies showed that dopamine receptors could regulate several ways of death of the tumor cell, including apoptosis, autophagy-induced death, and ferroptosis, which cannot only directly affect tumor behavior, but also limit tumor progress via activating tumor immunity. In this review, we focus mainly on the function of the dopamine receptor on Bio-behavior of tumor as a potential therapeutic target.

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“…Macrophage migration is one of the targets for the protective role of the brain and an increasing number of recent studies relate dopamine and inflammation and immunity. 57,73,74 Based on our cellular, molecular and pharmacological results, a possible mechanism explaining the protective effects of the brain in presence of bacteria is illustrated in the drawings-models of Fig. 6c, d.…”

Section: Discussionmentioning

confidence: 91%

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity

et al. 2020

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Infections have numerous effects on the brain. However, possible roles of the brain in protecting against infection, and the developmental origin and role of brain signaling in immune response, are largely unknown. We exploited a unique Xenopus embryonic model to reveal control of innate immune response to pathogenic E. coli by the developing brain. Using survival assays, morphological analysis of innate immune cells and apoptosis, and RNA-seq, we analyzed combinations of infection, brain removal, and tail-regenerative response. Without a brain, survival of embryos injected with bacteria decreased significantly. The protective effect of the developing brain was mediated by decrease of the infection-induced damage and of apoptosis, and increase of macrophage migration, as well as suppression of the transcriptional consequences of the infection, all of which decrease susceptibility to pathogen. Functional and pharmacological assays implicated dopamine signaling in the bacteria-brain-immune crosstalk. Our data establish a model that reveals the very early brain to be a central player in innate immunity, identify the developmental origins of brain-immune interactions, and suggest several targets for immune therapies.

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Potential Roles of Peripheral Dopamine in Tumor Immunity

Cited by 41 publications

References 99 publications

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

The Prospective Value of Dopamine Receptors on Bio-Behavior of Tumor

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity

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