puc-header

Nociceptor Neurons Decrease Cancer Immunosurveillance

38 Pages Posted: 22 Apr 2020 Sneak Peek Status: Under Review

See all articles by Mohammad Balood

Mohammad Balood

University of Montreal - Department of Pharmacology and Physiology

Maryam Ahmadi

University of Montreal - Department of Pharmacology and Physiology

Abdelilah Majdoubi

Université Laval - Department of Molecular Medicine

Tuany Eichwald

University of Montreal - Department of Pharmacology and Physiology

Hannah Merrison

Children's Hospital Boston - F.M. Kirby Neurobiology Center

Alexandre Parrin

Children's Hospital Boston - F.M. Kirby Neurobiology Center

Benjamin Doyle

Children's Hospital Boston - F.M. Kirby Neurobiology Center

Daniel Vermeer

Sanford Research

Chih-Chieh Wang

Cygnal Therapeutics

Monica Thanawala

Cygnal Therapeutics

Katiane Roversi

University of Montreal - Department of Pharmacology and Physiology

Sini C. Thomas

University of Montreal - Department of Pharmacology and Physiology

Corey R. Seehus

Children's Hospital Boston - F.M. Kirby Neurobiology Center

Simmie L. Foster

Massachusetts General Hospital

Alexandra Latini

Universidade Federal de Santa Catarina (UFSC)

Moutih Rafei

University of Montreal - Department of Pharmacology and Physiology

Manu Rangachari

Université Laval - Department of Molecular Medicine

Sonia Del Rincon

McGill University - Gerald Bronfman Department of Oncology

Chengyi J. Shu

Cygnal Therapeutics

Ronny Drapkin

University of Pennsylvania

Jacques Thibodeau

Université Laval - Department of Molecular Medicine

Clifford J. Woolf

Children's Hospital Boston - F.M. Kirby Neurobiology Center

Paola D. Vermeer

Sanford Research

Sebastien Talbot

University of Montreal - Department of Pharmacology and Physiology

More...

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.

Keywords: Nociceptor neurons, neuro-immunology, tumor innervation, melanoma, exhaustion, cytotoxic CD8 T cells, CGRP, TRPV1, QX-314, Botox.

Suggested Citation

Balood, Mohammad and Ahmadi, Maryam and Majdoubi, Abdelilah and Eichwald, Tuany and Merrison, Hannah and Parrin, Alexandre and Doyle, Benjamin and Vermeer, Daniel and Wang, Chih-Chieh and Thanawala, Monica and Roversi, Katiane and Thomas, Sini C. and Seehus, Corey R. and Foster, Simmie L. and Latini, Alexandra and Rafei, Moutih and Rangachari, Manu and Rincon, Sonia Del and Shu, Chengyi J. and Drapkin, Ronny and Thibodeau, Jacques and Woolf, Clifford J. and Vermeer, Paola D. and Talbot, Sebastien, Nociceptor Neurons Decrease Cancer Immunosurveillance. Available at SSRN: https://ssrn.com/abstract=3571293 or http://dx.doi.org/10.2139/ssrn.3571293
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Mohammad Balood

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Maryam Ahmadi

University of Montreal - Department of Pharmacology and Physiology

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Abdelilah Majdoubi

Université Laval - Department of Molecular Medicine

Canada

Tuany Eichwald

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Hannah Merrison

Children's Hospital Boston - F.M. Kirby Neurobiology Center

United States

Alexandre Parrin

Children's Hospital Boston - F.M. Kirby Neurobiology Center

United States

Benjamin Doyle

Children's Hospital Boston - F.M. Kirby Neurobiology Center

United States

Daniel Vermeer

Sanford Research ( email )

United States

Chih-Chieh Wang

Cygnal Therapeutics

United States

Monica Thanawala

Cygnal Therapeutics

United States

Katiane Roversi

University of Montreal - Department of Pharmacology and Physiology

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Sini C. Thomas

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Corey R. Seehus

Children's Hospital Boston - F.M. Kirby Neurobiology Center

United States

Simmie L. Foster

Massachusetts General Hospital

MA
United States

Alexandra Latini

Universidade Federal de Santa Catarina (UFSC)

Campus Reitor João David Ferreira Lima
Bairro Trindade
Florianopolis, Santa Catarina 88040
Brazil

Moutih Rafei

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Manu Rangachari

Université Laval - Department of Molecular Medicine

Canada

Sonia Del Rincon

McGill University - Gerald Bronfman Department of Oncology ( email )

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Chengyi J. Shu

Cygnal Therapeutics ( email )

United States

Ronny Drapkin

University of Pennsylvania ( email )

Philadelphia, PA 19104
United States

Jacques Thibodeau

Université Laval - Department of Molecular Medicine ( email )

Canada

Clifford J. Woolf

Children's Hospital Boston - F.M. Kirby Neurobiology Center ( email )

United States

Paola D. Vermeer

Sanford Research ( email )

United States

Sebastien Talbot (Contact Author)

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Click here to go to Cell.com

Paper statistics

Abstract Views
581
Downloads
232