Core Viewpoint - The study published in Nature highlights the role of cancer-induced nerve injury (CINI) in promoting resistance to anti-PD-1 therapy, emphasizing the importance of exploring cancer neuroscience for potential therapeutic targets [4][5][10]. Group 1: Cancer-Induced Nerve Injury (CINI) and Its Mechanism - CINI occurs when cancer cells damage the protective myelin sheath of peripheral nerves, leading to chronic inflammation and immune exhaustion, which ultimately results in resistance to immunotherapy [4][10]. - The study reveals that targeting CINI-related signaling pathways can reverse chronic inflammation and improve the efficacy of cancer immunotherapy [4][12]. Group 2: Tumor-Associated Nerves (TAN) and Immune Response - Tumor-associated nerves (TAN) are recognized as poor prognostic factors in various cancers, including skin squamous cell carcinoma, melanoma, gastric cancer, and pancreatic ductal adenocarcinoma [7][11]. - The interaction between cancer cells, TAN, and tumor immune activity is crucial, as damaged TAN can recruit immune cells that promote tumor progression and contribute to anti-PD-1 therapy resistance [8][11]. Group 3: Clinical Implications and Future Directions - The findings suggest that CINI and its associated chronic inflammation mediate the mechanisms of resistance to anti-PD-1 therapy, providing a basis for identifying biomarkers and developing therapeutic drugs to overcome resistance in cancer patients [12]. - Multi-faceted interventions targeting CINI pathways, such as denervation of tumors and blocking specific inflammatory signals, have shown potential in reversing anti-PD-1 resistance [11][12].

Core Viewpoint - The study reveals the complex interactions between neurons and glioblastoma cells, highlighting long-range cholinergic input as a significant factor in glioblastoma progression, providing new insights for cancer neuroscience research [4][8]. Group 1: Research Findings - The research team created a comprehensive brain connectivity map of glioblastoma (GBM) cells, demonstrating the influence of long-range cholinergic neurons on GBM progression [4][9]. - Local inputs are primarily glutamatergic, while long-distance connections exhibit diverse neurotransmitter characteristics, with cholinergic projections from the basal forebrain being a conserved input across different regions [7][9]. - The study identifies that acetylcholine release through muscarinic receptor CHRM3 promotes GBM growth in a circuit-specific manner, and blocking both acetylcholine and glutamate pathways results in an additive anti-tumor effect [10] [9]. Group 2: Implications for Treatment - Anticholinergic drug scopolamine inhibits GBM growth, while acetylcholinesterase inhibitor donepezil exacerbates the condition, indicating the potential for targeted therapies based on neurotransmitter signaling [4][7]. - The findings suggest that long-range neural regulatory pathways could serve as promising therapeutic targets for glioblastoma treatment [8].