The association between the neuroendocrine system and the tumor immune microenvironment: Emerging directions for cancer immunotherapy

This review summarizes emerging evidence that the neuroendocrine system is involved in the regulation of the tumor immune microenvironment (TIME) to influence cancer progression. The basis of the interaction between the neuroendocrine system and cancer is usually achieved by the infiltration of nerve fibers into the tumor tissue, which is called neurogenesis; the migration of cancer cells toward nerve fibers, which is called perineural invasion (PNI), and the neurotransmitters. In addition to the traditional role of neurotransmitters in neural communications, neurotransmitters are increasingly recognized as mediators of crosstalk between the nervous system, cancer cells, and the immune system. Recent studies have revealed that not only nerve fibers but also cancer cells and immune cells within the TIME can secrete neurotransmitters, exerting influence on both neurons and themselves. Furthermore, immune cells infiltrating the tumor environment have been found to express a wide array of neurotransmitter receptors. Hence, targeting these neurotransmitter receptors may promote the activity of immune cells in the tumor microenvironment and exert anti-tumor immunity. Herein, we discuss the crosstalk between the neuroendocrine system and tumor-infiltrating immune cells, which may provide feasible cancer immunotherapy options.