Oncolytic virus-driven immune remodeling revealed in mouse medulloblastomas at single cell resolution.
Oncolytic virus-driven immune remodeling revealed in mouse medulloblastomas at single cell resolution.
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DOI：
10.1016/j.omto.2023.07.006
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发表时间：
2023-09-21
期刊：
影响因子：
--
通讯作者：
Miller, Katherine E.
中科院分区：
文献类型：
--
作者：
Hedberg, Jack;Studebaker, Adam;Smith, Luke;Chen, Chun-Yu;Westfall, Jesse J.;Cam, Maren;Gross, Amy;Hernandez-Aguirre, Ilse;Martin, Alexia;Kim, Doyeon;Dhital, Ravi;Kim, Yeaseul;Roberts, Ryan D.;Cripe, Timothy P.;Mardis, Elaine R.;Cassady, Kevin A.;Leonard, Jeffrey;Miller, Katherine E.
针对肿瘤限制性感染进行修饰的溶瘤病毒是一种有前途的癌症免疫系统，但关于驱动其在肿瘤微环境中的活性和结果的因素仍有许多有待了解。在这里，我们报告说，溶瘤单纯疱疹病毒C134，以前发现发挥T细胞依赖性的疗效在小鼠模型的胶质母细胞瘤，发挥T细胞独立的疗效在小鼠模型的髓母细胞瘤，表明这种溶瘤病毒使用不同的机制，在不同的肿瘤。我们研究了C134在小鼠髓母细胞瘤中的行为，使用单细胞RNA测序以全转录组分辨率绘制C134诱导的细胞类型、时间点和髓母细胞瘤亚组模型的基因表达变化。我们的工作详细说明了大量溶瘤病毒诱导的髓母细胞瘤浸润免疫细胞的转录重塑，10个单核细胞和巨噬细胞亚群共同表现出对C134的M1样反应，并建议将C134作为髓母细胞瘤的潜在新疗法进行研究。米勒等人表明OV C134在不同的脑肿瘤中表现出不同的功效机制，延长了携带成神经管细胞瘤的小鼠的中位生存期，而不管T细胞是否存在，并诱导肿瘤免疫微环境的显著改变，特别是通过诱导M1样巨噬细胞应答。
Oncolytic viruses, modified for tumor-restricted infection, are a promising cancer immunotherapeutic, yet much remains to be understood about factors driving their activity and outcome in the tumor microenvironment. Here, we report that oncolytic herpes simplex virus C134, previously found to exert T cell-dependent efficacy in mouse models of glioblastoma, exerts T cell-independent efficacy in mouse models of medulloblastoma, indicating this oncolytic virus uses different mechanisms in different tumors. We investigated C134’s behavior in mouse medulloblastomas, using single cell RNA sequencing to map C134-induced gene expression changes across cell types, timepoints, and medulloblastoma subgroup models at whole-transcriptome resolution. Our work details substantial oncolytic virus-induced transcriptional remodeling of medulloblastoma-infiltrating immune cells, 10 subpopulations of monocytes and macrophages collectively demonstrating M1-like responses to C134, and suggests C134 be investigated as a potential new therapy for medulloblastoma. Miller et al. show that OV C134 exhibits different mechanisms of efficacy in different brain tumors, prolonging median survival of medulloblastoma-bearing mice regardless of T cell presence, and inducing significant alterations in the tumor immune microenvironment, particularly through induction of an M1-like macrophage response.
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影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
--
作者：
Currier MA;Sprague L;Rizvi TA;Nartker B;Chen CY;Wang PY;Hutzen BJ;Franczek MR;Patel AV;Chaney KE;Streby KA;Ecsedy JA;Conner J;Ratner N;Cripe TP
通讯作者：
Cripe TP
DOI：
10.4049/jimmunol.1301966
发表时间：
2013-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Griesinger AM;Birks DK;Donson AM;Amani V;Hoffman LM;Waziri A;Wang M;Handler MH;Foreman NK
通讯作者：
Foreman NK
影响因子：
5.2
作者：
Casciati, Arianna;Tanori, Mirella;Mancuso, Mariateresa
通讯作者：
Mancuso, Mariateresa