Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic

As a crucial component of the tumor microenvironment, the nervous system modulates tumor initiation, progression, and metastasis. Conversely, tumors actively hijack and reshape neural structures to activate nerve-dependent developmental and regenerative processes that promote their own growth and survival.

Despite extensive progress in tumor-neural crosstalk, the molecular mechanisms underlying neuro-immune coordination in peripheral nerve remodeling remain incompletely understood, and integrated strategies targeting this axis to overcome immunotherapy resistance are still lacking. This review comprehensively examines the phenotypic and functional remodeling of the peripheral nervous system within the tumor microenvironment, with a focus on neuro-immune crosstalk between neural cells, immune cells and cancer cells.

We systematically analyze phenotypic remodeling in neurons and glial cells, with particular emphasis on autonomic nerve differentiation, functional reprogramming of the neurotrophin family, and the regulatory roles of immune cells in these processes.