Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep 12;4(1):29-42.
doi: 10.1096/fba.2021-00066. eCollection 2022 Jan.

Neural regulations of the tumor microenvironment

Anthony C Restaino  1   2 , Paola D Vermeer  1   2
Affiliations

Neural regulations of the tumor microenvironment

Anthony C Restaino et al. FASEB Bioadv. .

Abstract

The identification of nerves in the tumor microenvironment has ushered in a new area of research in cancer biology. Numerous studies demonstrate the presence of various types of peripheral nerves (sympathetic, parasympathetic, sensory) within the tumor microenvironment; moreover, an increased density of nerves in the tumor microenvironment correlates with worse prognosis. In this review, we address the current understanding of nerve-mediated alterations of the tumor microenvironment and how they impact disease through a variety of processes, including direct nerve-cancer cell communication, alteration of the infiltrative immune population, and alteration of stromal components.

Keywords: cancer; immune escape; neuro‐immune communication; tumor innervation; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

Authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
β‐adrenergic signaling in tumor cells. Various studies have identified β‐adrenergic signaling as a mediator of tumor cell proliferation. Here we outline downstream components of the β‐adrenergic signaling pathway involved in these aspects of tumor biology. Created with BioRender.com
FIGURE 2
FIGURE 2
Sensory nerve signaling in tumor cells. Various studies have identified sensory neuropeptide signaling as a mediator of tumor cell proliferation and cancer progression. Here we outline downstream components of the sensory nerve signaling pathway involved in these aspects of tumor biology through substance P and CGRP signaling. Created with BioRender.com
FIGURE 3
FIGURE 3
Neural regulation of the cellular components of the tumor microenvironment. During development solid tumors become innervated with a variety of nerves. These nerves, in turn, interact with and regulate various components of the tumor microenvironment, including promoting angiogenesis, production of an immunosuppressive microenvironment, and direct promotion of cancer cell proliferation and metastasis. Created with BioRender.com
See this image and copyright information in PMC

References

    1. Duechler M, Peczek L, Zuk K, Zalesna I, Jeziorski A, Czyz M. The heterogeneous immune microenvironment in breast cancer is affected by hypoxia‐related genes. Immunobiol. 2014;219(2):158‐165. - PubMed
    1. Balsamo M, Manzini C, Pietra G, et al. Hypoxia downregulates the expression of activating receptors involved in NK‐cell‐mediated target cell killing without affecting ADCC. Eur J Immunol. 2013;43(10):2756‐2764. - PubMed
    1. Liu B, Wei C. Hypoxia induces overexpression of CCL28 to recruit treg cells to enhance angiogenesis in lung adenocarcinoma. J Environ Pathol Toxicol Oncol. 2021;40(1):65‐74. - PubMed
    1. So T, Takenoyama M, Mizukami M, et al. Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer. Cancer Res. 2005;65(13):5945‐5952. - PubMed
    1. Williams MM, Christenson JL, O'Neill KI, et al. MicroRNA‐200c restoration reveals a cytokine profile to enhance M1 macrophage polarization in breast cancer. NPJ Breast Cancer. 2021;7(1):64. - PMC - PubMed

LinkOut - more resources