Tan Qijia, Li Feng, Wang Jun, Liu Yi, Cai Yingqian, Zou Yuxi, Jiang Xiaodan
Department of Neurosurgery Center, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Guangzhou, China.
Department of Neurosurgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Clin Med Insights Oncol. 2024 Oct 16;18:11795549241285239. doi: 10.1177/11795549241285239. eCollection 2024.
For glioma patients, the long-term advantages of dendritic cells (DCs) immunization remain unknown. It is extremely important to develop new treatment strategies that enhance the immunotherapy effect of DC-based vaccines. DCs exposed to glioma stem cells (GSCs) are considered promising vaccines against glioma.
Glioma stem cells were isolated from mouse glioma GL261 cells (GCs). Both were subjected to severe (47°C) and mild (42°C) heat shock to induce immunogenic cell death (ICD). Membrane mobilization of calreticulin (CRT) and release of heat shock proteins (HSPs) were detected by flow cytometry. Dendritic cells were then exposed to heat-inactivated cells and co-culturing of T cells tested for immunotherapeutic efficacy in vitro. In vivo, we investigated the GSC targeting effect of the GSC-DC vaccine combined with CD47 blockade.
Heat shock induced ICD in GCs and GSCs, as indicated by significant release of calreticulin, HSP70, and HSP90. Heat shock condition ICD lysates induce maturation and activation-associated marker expression on monocyte-derived DCs. Accordingly, DCs pulsed with GCs and GSCs inactivated reduced colony formation, sphere formation, migration, and invasion of glioma and GSCs in vitro. Glioma stem cell-DC vaccine in combination with anti-CD47 antibody significantly enhanced survival in mice with glioma, induced production of interferon (IFN)-γ, and enhanced T-cell expansion in vivo. Of note, DCs pulsed with inactivated GSCs were more effective to control tumor growth than DCs pulsed with inactive GCs.
Severe heat shock induces ICD in vitro. These data showed that administration of anti-CD47 antibody combined with GSC-DC vaccine may represent an effective immunotherapeutic strategy for cancer patients in clinical.
对于胶质瘤患者，树突状细胞（DCs）免疫的长期优势尚不清楚。开发新的治疗策略以增强基于DC的疫苗的免疫治疗效果极为重要。暴露于胶质瘤干细胞（GSCs）的DCs被认为是有前景的抗胶质瘤疫苗。
从小鼠胶质瘤GL261细胞（GCs）中分离出胶质瘤干细胞。两者均经受重度（47°C）和轻度（42°C）热休克以诱导免疫原性细胞死亡（ICD）。通过流式细胞术检测钙网蛋白（CRT）的膜动员和热休克蛋白（HSPs）的释放。然后将树突状细胞暴露于热灭活细胞，并测试T细胞的共培养以评估体外免疫治疗效果。在体内，我们研究了GSC-DC疫苗联合CD47阻断的GSC靶向作用。
热休克诱导GCs和GSCs发生ICD，表现为钙网蛋白、HSP70和HSP90的显著释放。热休克条件下的ICD裂解物诱导单核细胞来源的DCs上成熟和激活相关标志物的表达。因此，用GCs和GSCs灭活脉冲处理的DCs在体外减少了胶质瘤和GSCs的集落形成、球体形成、迁移和侵袭。胶质瘤干细胞-DC疫苗联合抗CD47抗体显著提高了胶质瘤小鼠的生存率，诱导了干扰素（IFN）-γ的产生，并增强了体内T细胞的扩增。值得注意的是，用灭活的GSCs脉冲处理的DCs在控制肿瘤生长方面比用灭活的GCs脉冲处理的DCs更有效。
重度热休克在体外诱导ICD。这些数据表明，抗CD47抗体与GSC-DC疫苗联合给药可能是临床上癌症患者有效的免疫治疗策略。
