Emerging cancer−neuroscience and immuno−oncology insights reframe PNI as a neuro−immune niche, in which neurotrophic signaling (GDNF–RET, NGF–TrkA), Schwann−cell plasticity, and neuromodulators (adenosine via CD39/CD73–A2A; nociceptor−derived CGRP) calibrate tumor behavior and immune tone along cranial nerves. The gene discussed is GDNF; the disease is neoplasm.