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. 2021 Apr 12;7:76. doi: 10.1038/s41420-021-00450-y

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Nerves can secrete the neuroactive molecules that act on tumor cells, lymphocytes, and macrophages to promote tumor proliferation, invasion, angiogenesis, and inflammation. In turn, tumor cells migrate to nerves and damage them to induce the cancer-associated pain. Moreover, tumor cells secrete cytokines, which drive nerve reprogramming and regeneration. PNI perineural invasion.