Project description:Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems1-5. 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 antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating leukocytes and decreased the growth of tumours, nearly tripling the survival rate of mice that were inoculated with B16F10 melanoma cells. Conversely, CD8+ T cell exhaustion was rescued in sensory-neuron-depleted mice that were treated with local recombinant CGRP. As compared with wild-type CD8+ T cells, Ramp1-/- CD8+ T cells were protected against exhaustion when co-transplanted into tumour-bearing Rag1-deficient mice. Single-cell RNA sequencing of biopsies from patients with melanoma revealed that intratumoral RAMP1-expressing CD8+ T cells were more exhausted than their RAMP1-negative counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis. Overall, our results suggest that reducing the release of CGRP from tumour-innervating nociceptors could be a strategy to improve anti-tumour immunity by eliminating the immunomodulatory effects of CGRP on cytotoxic CD8+ T cells.

| S-EPMC9646485 | biostudies-literature

Nociceptor neurons affect cancer immunosurveillance [RNA-seq 3]

Project description:Sequecing tumor-innervating neurons

2022-08-10 | GSE205865 | GEO

Nociceptor neurons affect cancer immunosurveillance

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-10 | GSE205866 | GEO

Nociceptor neurons affect cancer immunosurveillance [RNA-seq 2]

Project description:Sequencing Neuron, melanoma and CD8 when culture alone or co-culture with one another

2022-08-10 | GSE205864 | GEO

Nociceptor neurons affect cancer immunosurveillance [RNA-seq 1]

Project description:Neuron, melanoma and CD8 co-cultures

2022-08-10 | GSE205863 | GEO

Expression data from FACS purified nociceptor neurons from peripheral sensory ganglia

Project description:The goal of this study was to analyze global gene expression in specific populations of nociceptor sensory neurons, the neurons that detect damaging/noxious stimuli. The dorsal root ganglia (DRG), trigeminal ganglia, and nodose ganglia are anatomically distinct peripheral sensory ganglia that contain nociceptors which innervate skin, gut, lungs, and other distinct organ tissues. We used flow cytometry to purify nociceptors from these ganglia and profiled their global gene expression signatures to compare gene expression between these different anatomically distinct nociceptors. Nav1.8-Cre were bred with Rosa26-TdTomato to generate Nav1.8-Cre/R26-TdTomato reporter progeny, where all peripheral nociceptor neurons are genetically marked with red fluroescence due to specific expression of the TTX- resistant sodium channel Nav1.8. Lumbar region dorsal root ganglia (DRG), trigeminal ganglia, and nodose ganglia were dissected from mice (3 mice were pooled/sample). Highly red fluorescent neurons were Facs purified, RNA extracted, and processed for microarray analysis.

2013-08-28 | E-GEOD-46546 | biostudies-arrayexpress

Expression data from FACS purified nociceptor neurons from peripheral sensory ganglia

2013-08-28 | GSE46546 | GEO