文章：

基于II类反式激活因子的免疫疗法在小鼠和人类胶质母细胞瘤中的效果有限

Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma

原文发布日期：30 December 2023

DOI: 10.3390/cancers16010193

类型: Article

开放获取: 是

英文摘要：

Background: The major histocompatibility complex type II is downregulated in glioblastoma (GB) due to the silencing of the major transcriptional regulator class II transactivator (CIITA). We investigated the pro-immunogenic potential of CIITA overexpression in mouse and human GB. Methods: The intracerebral growth of wildtype GL261-WT cells was assessed following contralateral injection of GL261-CIITA cells or flank injections with GL261-WT or GL261-CIITA cells. Splenocytes obtained from mice implanted intracerebrally with GL261-WT, GL261-CIITA cells or phosphate buffered saline (PBS) were transferred to other mice and subsequently implanted intracerebrally with GL261-WT. Human GB cells and (syngeneic) GB-infiltrating immune cells were isolated from surgical samples and co-cultured with GB cells expressing CIITA or not, followed by RT-qPCR assessment of the expression of key immune regulators. Results: Intracerebral vaccination of GL261-CIITA significantly reduced the subsequent growth of GL261-WT cells implanted contralaterally. Vaccination with GL261-WT or -CIITA subcutaneously, however, equivalently retarded the intracerebral growth of GL261 cells. Adoptive cell transfer experiments showed a similar antitumor potential of lymphocytes harvested from mice implanted intracerebrally with GL261-WT or -CIITA. Human GB-infiltrating myeloid cells and lymphocytes were not activated when cultured with CIITA-expressing GB cells. Tumor-infiltrating NK cells remained mostly inactivated when in co-culture with GB cells, regardless of CIITA. Conclusion: these results question the therapeutic potential of CIITA-mediated immunotherapy in glioblastoma.

摘要翻译： 

背景：在胶质母细胞瘤（GB）中，由于主要转录调节因子II类反式激活因子（CIITA）的沉默，主要组织相容性复合体II类表达下调。本研究探讨了在小鼠和人类GB中过表达CIITA的促免疫原性潜力。方法：在对侧注射GL261-CIITA细胞或侧腹注射GL261-WT或GL261-CIITA细胞后，评估野生型GL261-WT细胞的脑内生长情况。将从脑内植入GL261-WT、GL261-CIITA细胞或磷酸盐缓冲盐水（PBS）的小鼠获取的脾细胞转移至其他小鼠，随后这些小鼠脑内植入GL261-WT细胞。从手术样本中分离人类GB细胞及（同基因）GB浸润免疫细胞，并与表达或不表达CIITA的GB细胞共培养，随后通过RT-qPCR评估关键免疫调节因子的表达。结果：脑内接种GL261-CIITA细胞显著降低了随后对侧植入的GL261-WT细胞的生长。然而，皮下接种GL261-WT或GL261-CIITA细胞对GL261细胞脑内生长的抑制作用相当。过继性细胞转移实验显示，从脑内植入GL261-WT或GL261-CIITA细胞的小鼠获取的淋巴细胞具有相似的抗肿瘤潜力。人类GB浸润髓系细胞和淋巴细胞在与表达CIITA的GB细胞共培养时未被激活。无论CIITA表达与否，肿瘤浸润NK细胞在与GB细胞共培养时大多保持未激活状态。结论：这些结果对CIITA介导的免疫疗法在胶质母细胞瘤中的治疗潜力提出了质疑。

原文链接：

Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma