Neural regulation of tumor immune evasion and immunotherapy resistance: mechanisms and therapeutic strategies

Accumulating evidence places neural inputs alongside immune and stromal components as functional determinants of the tumor microenvironment (TME), with direct consequences for tumor behavior and therapeutic responsiveness. Neural cues within tumors can influence T-cell activity, myeloid phenotypes, and the spatial organization of immune cells, collectively creating conditions that facilitate immune evasion and compromise immunotherapeutic efficacy. This communication is reciprocal, as immune cells can also modify neural growth and plasticity, giving rise to a dynamic neuroimmune circuit. Here, we synthesize the cellular and molecular mechanisms linking tumor-associated neural remodeling to immune evasion and immunotherapy resistance, focusing on the sympathetic–β-adrenergic and sensory nerve–CGRP–RAMP1 pathways and their roles in shaping immune spatial architecture. We further discuss therapeutic opportunities arising from combined targeting of neuroimmune signaling and immune checkpoint blockade, and highlight their potential relevance for biomarker development and overcoming resistance in solid tumors.