Neurotransmitters: promising immune modulators in the tumor microenvironment

Xiao, Lushan; Li, Xunjun; Fang, Chuanfa; Yu, Jiang; Chen, Tao

doi:10.3389/fimmu.2023.1118637

Cited by 9 publications

(5 citation statements)

References 197 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…intermedia . Notably, GABA is an important inhibitory neurotransmitter in the body, and emerging data suggest that neurotransmitters can affect immune cells in the TME to regulate tumor progression [ 25 , 26 ]. Recent studies have confirmed that GABA and GABAB receptors, as potential tumor suppressors, have clear antitumor activity against liver cancer, pancreatic cancer, bile duct cancer, and colorectal cancer [ 25 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment

Zhou,

Qin,

et al. 2024

Exp Hematol Oncol

View full text Add to dashboard Cite

Background Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. Methods P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. Results Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. Conclusions Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment

Zhou,

Qin,

et al. 2024

Exp Hematol Oncol

View full text Add to dashboard Cite

show abstract

“…The authors found that this manipulation led to the accelerated growth of murine breast cancers. This sustained release of NE within tumor-influenced immune checkpoint proteins, such as PD-1, PD-L1, and FOXP3, is known to greatly inhibit the body’s antitumor immune actions [ 80 ]. Sympathetic denervation abrogated the oncogenic effect.…”

Section: Neural Regulation Of the Immune Systemmentioning

confidence: 99%

The Neuroimmune Axis and Its Therapeutic Potential for Primary Liver Cancer

Mandal,

Yadav,

Sheth

2024

IJMS

View full text Add to dashboard Cite

The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays a key role in primary liver diseases. Until recently, however, the impact of nerves on cancer development, progression, and metastasis has been unappreciated. This review highlights recent advances in understanding neuroanatomical networks within solid organs and their mechanistic influence on organ function, specifically in the liver and liver cancer. We discuss the interaction between the autonomic nervous system, including sympathetic and parasympathetic nerves, and the liver. We also examine how sympathetic innervation affects metabolic functions and diseases like nonalcoholic fatty liver disease (NAFLD). We also delve into the neurobiology of the liver, the interplay between cancer and nerves, and the neural regulation of the immune response. We emphasize the influence of the neuroimmune axis in cancer progression and the potential of targeted interventions like neurolysis to improve cancer treatment outcomes, especially for hepatocellular carcinoma (HCC).

show abstract

“…Neurotransmitters/neuropeptides such as ACh, GABA, serotonin (5-HT), NE, NPY, and neurotensin, which can be produced by tumor cells and immune cells inside the TLT, might affect cancer progression/metastasis through multiple signaling pathways (149,150). Neurotransmitters/neuropeptides and cytokines/chemokines that regulate tumor cell migration might provide an effective pharmacological approach for inhibiting cancer invasion/metastasis (151)(152)(153).…”

Section: Innervation Of Tltsmentioning

confidence: 99%

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

Boahen,

Hu,

Adams

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

The central nervous system (CNS) influences the immune system generally by regulating the systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas the peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions/connections. An imbalance between the components of the PNS might contribute to pathogenesis and the further development of certain diseases. In this review, we have explored the “thread” (hardwiring) of the connections between the immune system (e.g., primary/secondary/tertiary lymphoid tissues/organs) and PNS (e.g., sensory, sympathetic, parasympathetic, and enteric nervous systems (ENS)) in health and disease in vitro and in vivo. Neuroimmune cell units provide an anatomical and physiological basis for bidirectional crosstalk between the PNS and the immune system in peripheral tissues, including lymphoid tissues and organs. These neuroimmune interactions/modulation studies might greatly contribute to a better understanding of the mechanisms through which the PNS possibly affects cellular and humoral-mediated immune responses or vice versa in health and diseases. Physical, chemical, pharmacological, and other manipulations of these neuroimmune interactions should bring about the development of practical therapeutic applications for certain neurological, neuroimmunological, infectious, inflammatory, and immunological disorders/diseases.

show abstract

Neurotransmitters: promising immune modulators in the tumor microenvironment

Cited by 9 publications

References 197 publications

Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment

Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment

The Neuroimmune Axis and Its Therapeutic Potential for Primary Liver Cancer

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

Contact Info

Product

Resources

About