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- Title
Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression.
- Authors
Costa, Pedro A. C.; Silva, Walison N.; Prazeres, Pedro H. D. M.; Picoli, Caroline C.; Guardia, Gabriela D. A.; Costa, Alinne C.; Oliveira, Mariana A.; Guimarães, Pedro P. G.; Gonçalves, Ricardo; Pinto, Mauro C. X.; Amorim, Jaime H.; Azevedo, Vasco A. C.; Resende, Rodrigo R.; Russo, Remo C.; Cunha, Thiago M.; Galante, Pedro A. F.; Mintz, Akiva; Birbrair, Alexander
- Abstract
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.
- Subjects
MELANOMA; TUMOR-infiltrating immune cells; ACTION potentials; TUMOR microenvironment; CANCER invasiveness; DESIGNER drugs; SENSORY neurons
- Publication
Acta Neuropathologica Communications, 2021, Vol 9, Issue 1, p1
- ISSN
2051-5960
- Publication type
Article
- DOI
10.1186/s40478-021-01273-9