# Roles of Peripheral Nerves in Tumor Initiation and Progression

## TL;DR

This review explores how peripheral nerves and Schwann cells influence cancer development and progression, focusing on different tumor types.

## Contribution

The paper provides a comprehensive overview of the role of peripheral nerve innervation and Schwann cells in tumor progression.

## Key findings

- Peripheral nerve fibers are more abundant in tumors than in healthy tissues and influence cancer initiation and metastasis.
- Schwann cells in tumors resemble repair Schwann cells and may shape the tumor microenvironment by regulating immune responses.
- The role of innervation in hepatocarcinoma remains largely unexplored and requires further investigation.

## Abstract

In recent years, a long list of relevant studies has highlighted the engagement of the nervous system in the fine-tuning of tumor development and progression. Several authors have shown that different types of nerve fibres (sympathetic, parasympathetic/vagal or somatosensory fibres) may contribute to tumor innervation affecting cancer initiation, progression and metastasis. A large presence of nerve fibres is frequently observed in tumors with respect to the corresponding healthy tissues. In this regard, it is worth noting that in some cases a reduced innervation may associate with slow tumor growth in a tissue-specific manner. Current studies have begun to shed light over the role played in this specific process by Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system. SCs observed in cancer tissues share strong similarities with repair SCs that appear after nerve injury. A large body of research indicates that SCs may have a role in shaping the microenvironment of tumors by regulating the immune response and influencing their invasiveness. In this review, we summarize data relevant to the role of peripheral innervation in general, and of SCs in particular, in defining the progression of different tumors: melanoma that originate in the skin with mainly sensory innervation; pancreatic and liver-derived tumors (e.g., pancreatic adenocarcinoma and cholangiocarcinoma) with mainly autonomous innervation. We conclude by summarizing data regarding hepatocarcinoma (with anatomical predominance of small autonomic nerve fibres) in which the potential relationship between innervation and tumor progression has been little explored, and largely remains to be defined.