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

Acta Neuropathologica Communications

Jaime H. Amorim¹  Gabriela D. A. Guardia²  Pedro A. F. Galante²  Rodrigo R. Resende³  Mariana A. Oliveira³  Mauro C. X. Pinto⁴  Thiago M. Cunha⁵  Remo C. Russo⁶  Pedro P. G. Guimarães⁶  Vasco A. C. Azevedo⁷  Caroline C. Picoli⁸  Ricardo Gonçalves⁸  Alinne C. Costa⁸  Pedro H. D. M. Prazeres⁸  Walison N. Silva⁸  Pedro A. C. Costa⁸  Alexander Birbrair⁹  Akiva Mintz^1,10 

[1] Centro das Ciências Biológicas e da Saúde, Universidade Federal do Oeste da Bahia, Barreiras, BA, Brasil;Centro de Oncologia Molecular, Hospital Sirio-Libanes, Sao Paulo, SP, Brasil;Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil;Departamento de Farmacologia, Universidade Federal de Goiás, Goiânia, GO, Brasil;Departamento de Farmacologia, Universidade de São Paulo, Ribeirão Preto, SP, Brasil;Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil;Departamento de Genetica, Ecologia e Evolucao, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil;Departamento de Patologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil;Departamento de Patologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil;Department of Radiology, Columbia University Medical Center, New York, NY, USA;Department of Radiology, Columbia University Medical Center, New York, NY, USA;

关键词: Sensory neurons;    Tumor microenvironment;    Melanoma;    Neuronal activity;    Chemogenetics;   

DOI  :  10.1186/s40478-021-01273-9

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY