Godlewski Jakub, Farhath Mohamed, Ricklefs Franz L, Passaro Carmela, Kiel Klaudia, Nakashima Hiroshi, Chiocca E Antonio, Bronisz Agnieszka
Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
NeuroOncology Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Cancers (Basel). 2021 Mar 14;13(6):1287. doi: 10.3390/cancers13061287.
Oncolytic virus (OV) therapy, which is being tested in clinical trials for glioblastoma, targets cancer cells, while triggering immune cells. Yet OV sensitivity varies from patient to patient. As OV therapy is regarded as an anti-tumor vaccine, by making OV-infected cancer cells secrete immunogenic proteins, linking these proteins to transcriptome would provide a measuring tool to predict their sensitivity. A set of six patient-derived glioblastoma cells treated ex-vivo with herpes simplex virus type 1 (HSV1) modeled a clinical setting of OV infection. The cellular transcriptome and secreted proteome (separated into extracellular vesicles (EV) and EV-depleted fractions) were analyzed by gene microarray and mass-spectroscopy, respectively. Data validation and in silico analysis measured and correlated the secretome content with the response to infection and patient survival. Glioblastoma cells reacted to the OV infection in a seemingly dissimilar fashion, but their transcriptomes changed in the same direction. Therefore, the upregulation of transcripts encoding for secreted proteins implies a common thread in the response of cancer cells to infection. Indeed, the OV-driven secretome is linked to the immune response. While these proteins have distinct membership in either EV or EV-depleted fractions, it is their co-secretion that augments the immune response and associates with favorable patient outcomes.
溶瘤病毒（OV）疗法正在胶质母细胞瘤的临床试验中进行测试，该疗法靶向癌细胞，同时触发免疫细胞。然而，OV的敏感性因患者而异。由于OV疗法被视为一种抗肿瘤疫苗，通过使感染OV的癌细胞分泌免疫原性蛋白，将这些蛋白与转录组联系起来将提供一种预测其敏感性的测量工具。一组六个源自患者的胶质母细胞瘤细胞在体外接受1型单纯疱疹病毒（HSV1）治疗，模拟了OV感染的临床情况。分别通过基因微阵列和质谱分析细胞转录组和分泌蛋白质组（分为细胞外囊泡（EV）和不含EV的部分）。数据验证和计算机分析测量了分泌组内容物并将其与感染反应和患者生存率相关联。胶质母细胞瘤细胞对OV感染的反应看似不同，但其转录组朝着相同方向变化。因此，编码分泌蛋白的转录本的上调意味着癌细胞对感染反应中的一个共同线索。事实上，OV驱动的分泌组与免疫反应相关。虽然这些蛋白在EV或不含EV的部分中有不同的成员，但它们的共同分泌增强了免疫反应并与患者的良好预后相关。
