Abstract
The tumor microenvironment (TME), which is composed of various cell components and signaling molecules, plays an important role in the occurrence and progression of tumors and has become the central issue of current cancer research. In recent years, as a part of the TME, the peripheral nervous system (PNS) has attracted increasing attention. Moreover, emerging evidence shows that Schwann cells (SCs), which are the most important glial cells in the PNS, are not simply spectators in the TME. In this review article, we focused on the up-to-date research progress on SCs in the TME and introduced our point of view. In detail, we described that under two main tumor-nerve interaction patterns, perineural invasion (PNI) and tumor innervation, SCs were reprogrammed and acted as important participants. We also investigated the newest mechanisms between the interactions of SCs and tumor cells. In addition, SCs can have profound impacts on other cellular components in the TME, such as immune cells and cancer-associated fibroblasts (CAFs), involving immune regulation, tumor-related pain, and nerve remodeling. Overall, these innovative statements can expand the scope of the TME, help fully understand the significant role of SCs in the tumor-nerve-immune axis, and propose enlightenments to innovate antitumor therapeutic methods and future research.
Highlights
In recent decades, cancer research has exponentially expanded beyond the topic of cancer cells alone to include complex and extensive heterotypic interactions between cancer cells and the tumor microenvironment (TME) [1].erefore, intensive discussions have been made among the components of the TME, including cells, vasculature systems, widely existing extracellular matrix (ECM), and networks constituted by various signaling molecules [2,3,4]
Much emerging evidence has confirmed the crosstalk between cancer and the peripheral nervous system (PNS) [12, 13]. is link is usually related to the adverse outcomes of tumors and has become the hotspot of current research [14,15,16]
In the niche formed by tumor-nerve interactions in the process of cancer occurrence and development, what changes have occurred in Schwann cells (SCs) and what role will they play? What are the direct effects of SCs on tumor cells? In addition to tumor cells, which cell components in the TME can SCs interact with and what molecular mechanism is under it? e answers to these questions will help one comprehensively understand the role of nerves and their cellular contents in cancer progression, further expand the scope of the TME, and propose directions to innovate antitumor strategies and follow-up research
Summary
Cancer research has exponentially expanded beyond the topic of cancer cells alone to include complex and extensive heterotypic interactions between cancer cells and the tumor microenvironment (TME) [1]. For a long time, studies have mainly focused on the carcinogenic effects of neurons in the PNS [17, 18], which leads to an ignorance of glial cells. Compared to a great number of studies on glial cells of the central nervous system in the background of breast cancer or lung cancer brain metastasis [34, 35], SCs did not attract sufficient attention in the context of cancer. E answers to these questions will help one comprehensively understand the role of nerves and their cellular contents in cancer progression, further expand the scope of the TME, and propose directions to innovate antitumor strategies and follow-up research In the niche formed by tumor-nerve interactions in the process of cancer occurrence and development, what changes have occurred in SCs and what role will they play? What are the direct effects of SCs on tumor cells? In addition to tumor cells, which cell components in the TME can SCs interact with and what molecular mechanism is under it? e answers to these questions will help one comprehensively understand the role of nerves and their cellular contents in cancer progression, further expand the scope of the TME, and propose directions to innovate antitumor strategies and follow-up research
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