胶质母细胞瘤是中枢神经系统最恶性的肿瘤。目前基于手术、化疗、放疗以及最近采用选择性免疫学方法的治疗，都不幸地产生了令人沮丧的结果，不到2％的患者在5年后存活。因此，迫切需要新的治疗策略。在这里，我们报告了在动物实验系统中，用稳定表达MHC-II转录激活因子CIITA的胶质母细胞瘤GL261细胞疫苗接种后，对抗胶质母细胞瘤生长的前所未有的积极结果。接种了GL261-CIITA的小鼠会新表达MHC-II分子，并由于CD4 +和CD8 + T细胞的快速浸润而拒绝或强烈延缓肿瘤生长。重要的是，接种右脑半球GL261-CIITA细胞的小鼠强烈拒绝通过对侧脑半球注射的原父母GL261肿瘤，这表明不仅获得了抗肿瘤免疫记忆，而且还能够超越血脑屏障在大脑中迁移的免疫T细胞的能力。 GL261-CIITA细胞是一种有效的抗胶质母细胞瘤疫苗，在体内通过CIITA驱动的MHC-II表达和对肿瘤特异性CD4 + Th细胞的代理抗原提呈功能的获得，刺激了保护性适应性抗肿瘤免疫应答。这种前所未有的胶质母细胞瘤方法展示了突破性的免疫治疗策略的可行性，可以在临床应用中获得潜在的应用。版权所有©2023 Celesti、Gatta、Shallak、Chiaravalli、Cerati、Sessa、Accolla和Forlani。

Glioblastoma is the most malignant tumor of the central nervous system. Current treatments based on surgery, chemotherapy, and radiotherapy, and more recently on selected immunological approaches, unfortunately produce dismal outcomes, and less than 2% of patients survive after 5 years. Thus, there is an urgent need for new therapeutic strategies. Here, we report unprecedented positive results in terms of protection from glioblastoma growth in an animal experimental system after vaccination with glioblastoma GL261 cells stably expressing the MHC class II transactivator CIITA. Mice injected with GL261-CIITA express de novo MHC class II molecules and reject or strongly retard tumor growth as a consequence of rapid infiltration with CD4+ and CD8+ T cells. Importantly, mice vaccinated with GL261-CIITA cells by injection in the right brain hemisphere strongly reject parental GL261 tumors injected in the opposite brain hemisphere, indicating not only the acquisition of anti-tumor immune memory but also the capacity of immune T cells to migrate within the brain, overcoming the blood-brain barrier. GL261-CIITA cells are a potent anti-glioblastoma vaccine, stimulating a protective adaptive anti-tumor immune response in vivo as a consequence of CIITA-driven MHC class II expression and consequent acquisition of surrogate antigen-presenting function toward tumor-specific CD4+ Th cells. This unprecedented approach for glioblastoma demonstrates the feasibility of novel immunotherapeutic strategies for potential application in the clinical setting.Copyright © 2023 Celesti, Gatta, Shallak, Chiaravalli, Cerati, Sessa, Accolla and Forlani.