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Traditionally viewed as a tumor cell\u2010autonomous process, PNI is increasingly recognized as a dynamic phenomenon shaped by the tumor\u2013nerve\u2013stromal ecosystem. This review synthesizes recent advances to reframe neural invasion as a coordinated, multicellular process governed by reciprocal interactions within this niche. We delineate how stromal and immune components, including cancer\u2010associated fibroblasts, Schwann cells, immune cells, and the extracellular matrix, facilitate PNI through structural remodeling and biochemical signaling within the tumor\u2013nerve interface. These coordinated interactions drive nerve reorganization and local immune reprogramming, collectively establishing a permissive niche that supports tumor spread along neural routes. By integrating these interconnected mechanisms into a neuro\u2010ecological framework, we clarify how networked tumor\u2013stromal\u2013neural remodeling underlies neural dissemination. This perspective identifies therapeutic vulnerabilities within the neural microenvironment and suggests that disrupting bidirectional crosstalk between tumor cells and their stromal partners may offer strategies to limit neural spread and improve clinical outcomes.<\/jats:p>","DOI":"10.1002\/advs.76248","type":"journal-article","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T11:55:02Z","timestamp":1782647702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stromal Regulation of Tumor Perineural Invasion: A Multicellular and Neuro\u2010Ecological Perspective"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoyang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Nanfang Hospital Southern Medical University  Guangzhou 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