A 2025 Nature study reveals that tumors physically injure nearby nerves, triggering a nerve-repair response that suppresses anti-tumor immunity and causes resistance to anti-PD-1 checkpoint immunotherapy. Using head and neck squamous cell carcinoma and melanoma models — plus human patient cohorts — researchers showed that injured nerves release signals that recruit immunosuppressive macrophages and exclude cytotoxic T cells from tumors. Blocking nerve injury signals or promoting nerve regeneration restored immune activity and dramatically improved responses to anti-PD-1 therapy in preclinical models. These findings identify cancer-induced nerve injury as a previously unrecognized mechanism of immunotherapy resistance and suggest that targeting the neuro-immune axis could overcome treatment failure in multiple cancer types.
