Abstract
The nervous and immune systems, though traditionally studied as separate entities, are now recognized as deeply interconnected networks that jointly regulate tumor initiation, progression, and therapeutic response. Neural elements extend into the tumor microenvironment where they interact with immune cells, shaping processes such as proliferation, invasion, and metastasis. Through neurotransmitters, neuropeptides, and bidirectional signaling with the brain, nerves influence leukocyte recruitment, functional activity, and immune tone. Stress, circadian disruption, and gut–brain interactions further modulate antitumor immunity, underscoring the complexity of this axis. Evidence indicates that neuronal signaling contributes not only to cancer-related symptoms, including pain, but also to treatment outcomes in chemotherapy, radiotherapy, and immunotherapy. Neural markers may serve as prognostic tools, while targeted modulation of neural transmission could enhance antitumor responses. However, the field faces significant challenges, including cellular diversity, spatiotemporal complexity, and limitations of animal models. Advances in molecular biology, bioinformatics, and interdisciplinary collaboration are essential to unravel these mechanisms. Exploring the neuro-immune-cancer axis holds promise for novel therapeutic strategies that integrate neuroscience, immunology, and oncology,aiming to improve both quality of life and survival in patients with cancer. GRAPHICAL ABSTRACT: [Image: see text]