Macrophage neuronal crosstalk in the tumor microenvironment

  • Merad, Miriam (PI)
  • Casanova, María M. (CoPI)

Project Details

Description

Abstract

The autonomous nervous system (ANS) includes the sympathetic nervous system (SNS), the parasympathetic (PNS) and the enteric nervous system (ENS). Catecholamines and adrenergic receptors have been shown to promote the recruitment of leukocytes within tissues and therefore modulate tissue integrity and innate immunity [1]. The Merad’s group has also shown that in steady-state conditions macrophages located in the intestinal muscle layer localize in close apposition with intestinal neurons and produce neuromodulators, which promote the peristaltic activity of enteric neurons thereby regulating intestinal transit time [2]. Macrophages represent one of the major population of the tumor and in an effort to promote tissue healing, are thought to lead to immune suppression and progression of many tumors [3]. Importantly, the autonomic nerve fibers present in the prostate gland were found to regulate prostate cancer development and dissemination in mouse models [4]. Based on the observation that macrophages and neurons colocalize and modulate their reciprocal function, we raise the fundamental question of whether macrophages recruited into the tumor via adrenergic signals further communicate with emerging neural networks to promote tumor progression, and propose to study the nature and function of this communication within the tumor environment.

  • Scheiermann, C., et al. Immunity,2012.37(2).
  • Muller, P.A., et al. Cell,2014.158(2).
  • Lavin, Y. and Merad, M. Cancer Immunol Res, 2013. 1(4).
  • Magnon, C., et al. Science, 2013. 341(6142).
StatusFinished
Effective start/end date1/01/1531/12/17

Funding

  • Human Frontier Science Program

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