Neuroimmune crosstalk in cancer: emerging immunotherapeutic opportunities
TL;DR
A review of progression from tumor-induced neural remodeling and neural-like cell states to the sensory, autonomic, enteric, and systemic neuroendocrine axes that regulate antitumor immunity and how spatial omics resolves these interactions in situ is considered.
Abstract
Abstract The nervous system is increasingly recognized as an active regulatory layer of the tumor microenvironment. Tumors remodel local innervation, engage peripheral and central neural circuits, and mobilize neurotransmitters, neuropeptides, neurotrophic cues, and systemic neuroendocrine outputs that influence growth, invasion, immune evasion, therapeutic response, and toxicity. Tumor and stromal cells can also adopt neural-like phenotypes, extending tumor-neural communication beyond anatomically defined nerves. A unifying model is emerging: homeostatic neural inputs may support tissue integrity and immune surveillance, whereas tumor-activated or tumor-injured pathways can promote immune escape, dissemination, and immunotherapy resistance. This review follows that progression from tumor-induced neural remodeling and neural-like cell states to the sensory, autonomic, enteric, and systemic neuroendocrine axes that regulate antitumor immunity. We then consider how spatial omics resolves these interactions in situ and how neuroimmune pathways may be targeted to improve immunotherapy efficacy while limiting immune-related adverse events. Together, these advances position cancer neuroimmunology as a framework for interpreting tumor ecosystems and developing neuro-informed immunotherapies.