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• W3028340324 abstract "Tumor denervation limits cancer growth, but the mechanisms behind this are unknown. We find that malignant melanoma cells interact with pain-initiating nociceptor neurons by increasing neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. In turn, nociceptor-produced neuropeptides increase exhaustion of cytotoxic T cells (PD1+Lag3+Tim3+INFγ-), limiting their capacity to eliminate melanoma cells. Genetic TRPV1 or NaV1.8 lineage ablation, local pharmacological silencing as well as blockade of vesicle release from tumor-innervating nociceptors enhance tumor-infiltrating leukocyte (TIL) numbers and increase survival of mice subject to orthotropic melanoma inoculation, blunting tumor growth and TIL exhaustion. We conclude that reducing neuropeptide release from tumor-innervating nociceptors, by eliminating their immunomodulatory action on cytotoxic CD8 T cell, may be a useful therapeutic intervention to boost immune surveillance." @default.
• W3028340324 created "2020-05-29" @default.
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• W3028340324 date "2020-01-01" @default.
• W3028340324 modified "2023-10-01" @default.
• W3028340324 title "Nociceptor Neurons Decrease Cancer Immunosurveillance" @default.
• W3028340324 doi "https://doi.org/10.2139/ssrn.3571293" @default.
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