中枢神经系统远程启动及调控舌鳞癌微环境程序性坏死的作用机制

恶性肿瘤的许多行为具有胚胎发育的特征与程序性调控的印迹。近年发现，中枢神经系统对机体具有更广泛的主动、远程调控能力。肿瘤浸润神经可以调控炎性微环境，但机制未明。最新发现，中枢神经系统来源细胞可能经血循环直接进入外周肿瘤。我们发现，舌鳞癌通过程序性坏死释放IL-1β为主导的损伤相关分子模式塑造炎性微环境，促进颈淋巴转移，这种程序性坏死如何被启动及调控？进一步发现程序性坏死周围大量神经纤维浸润，舌鳞癌神经浸润密度与患者总生存负相关。率先提出，中枢神经系统可能与微环境浸润神经对话，远程启动舌鳞癌程序性坏死。拟首先探讨舌鳞癌浸润神经对微环境程序性坏死的调控机制，进而在神经细胞迁移、神经免疫复合信号等方面探讨中枢神经与舌鳞癌神经远程对话机制，在分子功能可视化水平阐明舌鳞癌微环境多级别程序调控，最后阻断“中枢神经-舌鳞癌神经-程序性坏死-慢性炎症”通路，探讨对颈淋巴转移防治作用，为舌鳞癌治疗提供新靶点

The behavior of malignant tumor mimics features in embryogenesis development and present trace of programmed regulation. Recently, it was reported that central nervous system can regulate more extensively and remotely than we knew before. Tumor infiltrating nerve could regulate inflammatory tumor microenvironment, but the mechanism is uncertain. Most recently, it was demonstrated that progenitor cells from central nervous system migrated into peripheral tumors. Our previous study showed that tongue squamous cell carcinoma released damage associated molecular patterns by the necroptosis to build up inflammatory microenvironment, then to promote lymph node metastasis. How did the necroptosis in TSCC microenvironment initiated and regulated? We further demonstrated that the area of necroptosis in TSCC were surrounded by nerve infiltration, and that nerve density in TSCC was associated with worse overall survival of TSCC patients. Based on these results, we propose that central nervous system can cross-talk with local infiltrated nerve in TSCC, to initiate and regulate necroptosis in TSCC microenvironment. We will at first investigate the regulation of necroptosis by TSCC nervous system, then investigate the remote regulation of TSCC nervous system by central nervous system through progenitor cell migration, nervous or immune signal transduction, to illustrate the multi-grade regulation of TSCC inflammatory microenvironment at molecular functional visualization level. At last, we will stop the multi-grade workshop of “central nervous system-TSCC nervous system-necroptosis-inflammatory microenvironment” to evaluate its significance in prevention and treatment of TSCC lymph node metastasis.