The Bridging Role of Schwann Cells in the Interaction between Tumors and the Nervous System: A Potential Target for Cancer Therapy

Nerves are important components of the tumor microenvironment and can regulate the progression of various solid tumors. Tumor innervation (TIN) and perineural invasion (PNI) are the two main modes of interaction between tumors and the nervous system. The former simulates neurogenesis or axonogenesis during neural development, whereas the latter causes neuroinflammation during nerve injury. As the principal glial cells of the peripheral nervous system, Schwann cells (SC) are easily hijacked and utilized by cancer cells due to their high plasticity and versatility. Whether TIN or PNI occurs in a tumor, SCs are believed to be associated with these processes, which indicate that SCs may be a target for cancer neurotherapy. This review focuses on elucidating the interactions between tumors and the peripheral nervous system and the underlying mechanisms involved. Specifically, we delineated the pivotal role of SCs in TIN, PNI, cancer pain, and the immunosuppressive microenvironment. Furthermore, we compared the advantages and disadvantages of several preclinical trials that have exploited the nervous system to treat cancer and discussed the importance of SCs as a new target in cancer neuroscience research. We hope that this review will contribute to a deeper understanding of the significant involvement of SCs within the tumor-neuroimmune axis and provide novel insights for innovative antitumor therapies.