Background/Objectives:Emerging studies have indicated the importance of intra-tumoral neuronal signals in tumor progression and immune modulation. However, there is limited insight into neuroimmune crosstalk, and the molecules involved are largely unknown. This study investigates the relationship between tumor-derived neuropeptides and immune modulation in head and neck squamous cell carcinoma (HNSC).Methods:By utilizing neuropeptide databases and web tools leveraging TCGA data, neuropeptides’ expression and their associations with neurotrophic factors, immune cell infiltration, and immune checkpoints were analyzed, followed by survival analysis.Results:Over half of the neuropeptides were expressed in HNSC, with 16% exhibiting differential expression compared to normal counterparts. Notably, differentially expressed neuropeptides showed significant correlations with neurotrophic factors, immune cell infiltration, and checkpoint genes. Further, their expression was significantly different in responder and non-responder patient samples subjected to immune checkpoint therapy. Neuropeptide genes—PTHLH, NMB, GAST, APLN, and LYNX1—were identified and emerged as crucial mediators in neuroimmune crosstalk. Additionally, the neurotrophic gene NTRK1 exhibited extensive correlation with immune checkpoint genes, underscoring the prevalence of neuroimmune crosstalk in HNSC.Conclusions:These findings shed light on the role of tumor-derived neuropeptides in neuroimmune regulation in HNSC, offering valuable insights for future studies to decode the cancer neuroscience of HNSC progression and therapy.
背景/目的：近期研究表明，肿瘤内神经元信号在肿瘤进展和免疫调节中具有重要作用。然而，目前对神经免疫交互作用的认知有限，且相关分子机制尚不明确。本研究旨在探讨头颈部鳞状细胞癌（HNSC）中肿瘤源性神经肽与免疫调节的关系。 方法：通过整合神经肽数据库及基于TCGA数据的网络分析工具，系统分析了神经肽的表达模式及其与神经营养因子、免疫细胞浸润和免疫检查点之间的关联，并进一步开展了生存分析。 结果：超过半数的神经肽在HNSC中表达，其中16%的神经肽相较于正常组织呈现差异表达。值得注意的是，差异表达的神经肽与神经营养因子、免疫细胞浸润及检查点基因均存在显著相关性。在接受免疫检查点治疗的患者样本中，应答者与非应答者间的神经肽表达存在显著差异。研究鉴定出PTHLH、NMB、GAST、APLN和LYNX1等神经肽基因，这些基因成为神经免疫交互作用的关键介质。此外，神经营养基因NTRK1与免疫检查点基因呈现广泛相关性，进一步证实了神经免疫交互在HNSC中的普遍性。 结论：本研究揭示了肿瘤源性神经肽在HNSC神经免疫调控中的作用，为未来深入解析HNSC进展与治疗中的癌症神经科学机制提供了重要线索。
肿瘤(癌症)患者之家