MiPEP133通过激活CD8+ T细胞增强鼻咽癌的抗肿瘤免疫
MiPEP133 enhances anti-tumor immunity in nasopharyngeal carcinoma by activating CD8 + T cells.
文献信息
| PMID | 42778929 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Mingjing Zhu |
| 作者单位 | Department of Radiation Oncology, Guangxi Tumor Radiation Therapy Clinical Medical Research Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China. |
| 期刊 | Journal of translational medicine |
| SCI 分区 | Q1 |
| IF | 8.8 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 鼻咽癌 |
中文摘要
背景： 肿瘤免疫微环境（TIME）的激活对于控制鼻咽癌（NPC）进展至关重要。本研究旨在确定miPEP133作为NPC治疗的新治疗靶点。
方法： 采用RNA-Seq评估miPEP133对NPC细胞和T细胞相关信号通路的影响。IHC检测人NPC组织中miPEP133蛋白表达。功能实验评估miPEP133在抗肿瘤免疫中的作用。将NPC细胞与T细胞共培养，通过流式细胞术、ELISA和皮下异种移植模型检测miPEP133对CD8+ T细胞活化、细胞毒性因子分泌和DC成熟的影响。免疫荧光（IF）、ELISA和Western blot评估miPEP133对NPC细胞免疫原性的影响。最后，电子显微镜、IF、Western blot和RT-qPCR系统验证了miPEP133在NPC细胞中的分子机制及其对T细胞的免疫调节作用。
结果： 本研究证实，NPC中miPEP133表达与CD8+ T细胞介导的抗肿瘤免疫呈正相关，并可能作为生存的独立预后因素。高miPEP133增加CD8+ T细胞浸润，增强CD8+ T细胞分泌颗粒酶B、IFN-γ和IL-2，并促进DC成熟。此外，miPEP133通过内质网应激增强肿瘤细胞抗原呈递。在裸鼠异种移植模型中，miPEP133显著抑制肿瘤生长，进一步验证了其增强抗肿瘤免疫的作用。机制上，miPEP133通过调节STING通路激活I型干扰素反应，随后通过JAK1/STAT1/STAT4轴重新激活T细胞免疫。
结论： NPC细胞中miPEP133过表达显著增强CD8+ T细胞介导的免疫，揭示了一种新的抗肿瘤机制。这些发现表明miPEP133在塑造NPC免疫微环境中起关键作用，突显了其治疗潜力。
英文摘要
BACKGROUND: Activation of the tumor immune microenvironment (TIME) is crucial for controlling nasopharyngeal carcinoma (NPC) progression. This study aims to identify miPEP133 as novel therapeutic targets for NPC treatment.
METHODS: RNA-Seq was used to assess miPEP133's effect on NPC cells and T-cell-related signaling pathways. IHC measured miPEP133 protein expression in human NPC tissues. Functional assays evaluated miPEP133's role in anti-tumor immunity. NPC cells were co-cultured with T cells to examine miPEP133's impact on CD8 + T-cell activation, cytotoxic factor secretion, and DC maturation via flow cytometry, ELISA, and a subcutaneous xenograft model. Immunofluorescence (IF), ELISA, and Western blot assessed miPEP133's effect on NPC cell immunogenicity. Finally, electron microscopy, IF, Western blot, and RT-qPCR systematically verified miPEP133's molecular mechanism in NPC cells and its immunomodulatory effects on T cells.
RESULTS: This study confirmed that miPEP133 expression in NPC was positively correlated with CD8 + T-cell-mediated anti-tumor immunity and may serve as an independent prognostic factor for survival. High miPEP133 increased CD8 + T-cell infiltration, enhanced secretion of Granzyme B, IFN-γ, and IL-2 from CD8 + T cells, and promoted DC maturation. Moreover, miPEP133 boosted tumor cell antigen presentation via endoplasmic reticulum stress. In a nude mouse xenograft model, miPEP133 significantly inhibited tumor growth, further validating its role in enhancing anti-tumor immunity. Mechanistically, miPEP133 activated type I interferon responses by regulating the STING pathway, subsequently reactivating T-cell immunity via the JAK1/STAT1/STAT4 axis.
CONCLUSIONS: MiPEP133 overexpression in NPC cells significantly enhances CD8 + T-cell-mediated immunity, revealing a novel anti-tumor mechanism. These findings demonstrate miPEP133's critical role in shaping the NPC immune microenvironment, highlighting its therapeutic potential.