Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland.
Department of Quantitative Biomedicine, University of Zurich, 8057 Zurich, Switzerland; Biomedical Informatics, University Hospital of Zurich, 8057 Zurich, Switzerland.
Cancer Cell. 2021 Mar 8;39(3):394-406.e4. doi: 10.1016/j.ccell.2020.12.022. Epub 2021 Jan 21.
Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex 1 virus (HSV-1) approved for cancer therapy. We investigate its effect on the clinical, histological, single-cell transcriptomic, and immune repertoire level using repeated fine-needle aspirates (FNAs) of injected and noninjected lesions in primary cutaneous B cell lymphoma (pCBCL). Thirteen patients received intralesional T-VEC, 11 of which demonstrate tumor response in the injected lesions. Using single-cell sequencing of the FNAs, we identify the malignant population and separate three pCBCL subtypes. Twenty-four hours after the injection, we detect HSV-1 transcripts in malignant and nonmalignant cells of the injected lesion but not of the noninjected lesion. Oncolytic virotherapy results in a rapid eradication of malignant cells. It also leads to interferon pathway activation and early influx of natural killer cells, monocytes, and dendritic cells. These events are followed by enrichment in cytotoxic T cells and a decrease of regulatory T cells in injected and noninjected lesions.
替莫唑胺（Temozolomide）是一种经基因修饰的单纯疱疹病毒 1 型（HSV-1），已被批准用于癌症治疗。我们使用原发性皮肤 B 细胞淋巴瘤（pCBCL）注射和未注射病变的重复细针抽吸（FNA），研究了其对临床、组织学、单细胞转录组和免疫库水平的影响。13 名患者接受了瘤内 T-VEC 治疗，其中 11 名患者在注射部位的病变中显示出肿瘤反应。通过 FNA 的单细胞测序，我们鉴定出恶性细胞群，并将 pCBCL 分为三个亚型。注射后 24 小时，我们在注射部位的恶性和非恶性细胞中检测到 HSV-1 转录本，但在未注射部位的病变中未检测到。溶瘤病毒治疗可迅速清除恶性细胞。它还导致干扰素通路的激活和自然杀伤细胞、单核细胞和树突状细胞的早期涌入。这些事件之后，注射和未注射病变中的细胞毒性 T 细胞增加，调节性 T 细胞减少。
