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Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

Pedro A C Costa1, Walison N Silva1, Pedro H D M Prazeres1

  • 1Departamento de Patologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.

Acta Neuropathologica Communications
|November 17, 2021
PubMed

Insights

Sensory neurons influence melanoma progression. Inhibiting their activity accelerates tumor growth, while overstimulating them slows it and enhances anti-tumor immunity, suggesting therapeutic potential.

Area of Science:

  • Neuroscience
  • Oncology
  • Immunology

Background:

  • Sensory neurons are increasingly recognized as components of the tumor microenvironment.
  • The role of sensory neuronal activity in regulating tumor progression, particularly melanoma, is not well understood.

Purpose of the Study:

  • To investigate the impact of sensory neuronal activity on melanoma growth, angiogenesis, and immune surveillance.
  • To explore the therapeutic potential of modulating sensory neuron activity in melanoma.

Main Methods:

  • Utilized Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to manipulate sensory neuron firing in melanoma models.
  • Assessed melanoma growth, angiogenesis, and immune cell infiltration.
  • Conducted retrospective in silico analysis of human melanoma biopsies.

Main Results:

  • Inhibition of sensory neurons accelerated melanoma growth and angiogenesis.
  • Overstimulation of sensory neurons reduced tumor growth and angiogenesis.
  • Sensory neuron overactivation enhanced anti-tumor immune surveillance by increasing lymphocytes and decreasing suppressive cells.
  • Increased expression of sensory neuron-related genes in human melanoma correlated with improved survival.

Conclusions:

  • Sensory neuronal activity significantly regulates melanoma progression.
  • Modulating sensory neuron activity holds promise as a therapeutic strategy for improving outcomes in melanoma patients.
Keywords:
ChemogeneticsMelanomaNeuronal activitySensory neuronsTumor microenvironment

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