瑞士苏黎世大学Reinhard Dummer研究组揭示溶瘤病毒疗法介导的抗肿瘤反应。该项研究成果于2021年1月21日在线发表在《癌细胞》杂志上。

研究人员表示，Talimogene laherparepvec（T-VEC）是一种经基因修饰的单纯疱疹病毒1（HSV-1），已批准用于癌症治疗。

研究人员在原发性皮肤B细胞淋巴瘤（pCBCL）中研究了注射该病毒对临床、组织学、单细胞转录组学和免疫组化水平的影响。13例患者接受了病灶内T-VEC，其中11例在注射的病灶中显示出肿瘤反应。通过单细胞测序，研究人员确定了恶性人群并分离了三种pCBCL亚型。

注射后二十四小时，研究人员在注射部位的恶性和非恶性细胞中检测到HSV-1 T-VEC转录本，但未注射部位则没有。溶瘤病毒疗法可迅速根除恶性细胞。它还导致干扰素途径活化和天然杀伤细胞、单核细胞和树突状细胞的早期汇集。这些事件之后，细胞毒性T细胞发生富集，并且调节性T细胞减少。

附：英文原文

Title: Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective

Author: Egle Ramelyte, Aizhan Tastanova, Zsolt Balázs, Desislava Ignatova, Patrick Turko, Ulrike Menzel, Emmanuella Guenova, Christian Beisel, Michael Krauthammer, Mitchell Paul Levesque, Reinhard Dummer

Issue&Volume: 2021-01-21

Abstract: 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-needleaspirates (FNAs) of injected and noninjected lesions in primary cutaneous B cell lymphoma(pCBCL). Thirteen patients received intralesional T-VEC, 11 of which demonstrate tumorresponse in the injected lesions. Using single-cell sequencing of the FNAs, we identifythe malignant population and separate three pCBCL subtypes. Twenty-four hours afterthe injection, we detect HSV-1T-VEC transcripts in malignant and nonmalignant cells of the injected lesion but not ofthe noninjected lesion. Oncolytic virotherapy results in a rapid eradication of malignantcells. It also leads to interferon pathway activation and early influx of naturalkiller cells, monocytes, and dendritic cells. 

DOI: 10.1016/j.ccell.2020.12.022

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30670-X