Nociceptor neurons affect cancer immunosurveillance

Abstract Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems 1–5 . Whether the neo-innervation of tumours by pain-initiating sensory neurons affects cancer immunosurveillance remains unclear. Here we show that melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. Calcitonin gene-related peptide (CGRP)—one such nociceptor-produced neuropeptide—directly increases the exhaustion of cytotoxic CD8 + T cells, which limits their capacity to eliminate melanoma. Genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors and…

• DM
  Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

  Award: R35NS105076
• UO
  University of Pennsylvania
• CR
  Cancer Research Society
• FB
  Fondation Brain Canada
• CD
  Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

  Award: 88887
• AF
  Azrieli Foundation
• NI
  National Institutes of Health

  Awards: 5P20GM103548, R35NS105076, P20GM103620
• CI
  Canadian Institutes of Health Research

  Awards: 461275, 407016, 461274, 30017
• NS
  Natural Sciences and Engineering Research Council of Canada

  Awards: RGPIN-2019-06824, RGPIN-2019