Disrupting neuro-immune feedback loops: novel targets to amplify cancer immunotherapy

Nervous system and immune system have tight interactions that modulate both nerves and immune cells' activities. The interplay between the nervous and immune systems within the tumor microenvironment is a critical yet underexplored determinant of cancer immunotherapy efficacy. This review presents a new model called the Neuro-Immune Feedback Loop, which suggests that two-way communication (like the immunosuppressive effects of norepinephrine and the influence of cytokines on nerve activity) creates self-perpetuating cycles that tumors use to avoid immune responses. We compile evidence regarding neurotransmitters (such as dopamine), neuropeptides (like CGRP) to suggest innovative strategies to disrupt the immune-nerve loops. The current review proposes that context-sensitive neuro-immune switches (for instance, the dual functions of GABA) and multi-target therapies (such as CRISPR-modified neurons combined with immune checkpoint inhibitors (ICIs) could enhance immunotherapy effectiveness. By connecting neuroscience with immunology and oncology, this review aims to provide a roadmap for overcoming resistance to immunotherapies, presenting testable ideas and a new approach for precision cancer treatment. Literature search: PubMed, Scopus, and Web of Science were searched for relevant studies published between January 2000 and March 2026, with emphasis on recent publications (2024-2026) related to neuro-immune interactions in cancer.