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

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Artigo de periódico

Título alternativo

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Membros da banca

Resumo

Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons’ firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons’ activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons’ activity may provide a valuable tool to improve melanoma patients’ outcomes.

Abstract

Assunto

Células Receptoras Sensoriais, Microambiente Tumoral, Melanoma

Palavras-chave

Sensory neurons, Tumor microenvironment, Melanoma, Neuronal activity, Chemogenetics

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Curso

Endereço externo

https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01273-9#rightslink

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