Zhang Wen, Hu Xiao, Liang Jing, Zhu Yujie, Zeng Beibei, Feng Lin, Zhao Changyun, Liu Shangmei, Liu Binlei, Zhang Kaitai
Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Mol Ther Oncolytics. 2020 Jan 11;16:158-171. doi: 10.1016/j.omto.2019.12.012. eCollection 2020 Mar 27.
Oncolytic viruses are promising immunoreagents. Numerous studies have shown that oncolytic virotherapy is effective for many tumors. Herein, we investigated the therapeutic effect of oHSV2, an oncolytic type 2 herpes simplex virus, on mouse colon carcinoma. The antitumor efficacy of oHSV2 was observed in both unilateral and bilateral colon cancer models. oHSV2 effectively eliminated tumors and prolonged the survival of mice without side effects. Additionally, treatment with oHSV2 effectively prevented the growth of rechallenged tumors and distant implanted tumors. The specific killing ability of splenic immune cells to tumor cells was enhanced. oHSV2 treatment effectively reduced the content of inhibitory immune cells (regulatory T cells [Tregs] and myeloid-derived suppressor cells [MDSCs]) and increased the content of positive immune cells (natural killer [NK], CD8 T, and dendritic cells [DCs]) in the spleen. Moreover, treatment with oHSV2 remodeled the tumor immune microenvironment. In summary, treatment with oHSV2 can effectively eliminate primary tumors, generate tumor-specific immunity, and elicit immune memory to inhibit tumor recurrence and metastasis. Furthermore, this virotherapy can reshape the immune status of the spleen and tumor microenvironment in mice, which can further improve the therapeutic antitumor effect.
溶瘤病毒是很有前景的免疫试剂。大量研究表明，溶瘤病毒疗法对许多肿瘤有效。在此，我们研究了溶瘤2型单纯疱疹病毒（oHSV2）对小鼠结肠癌的治疗效果。在单侧和双侧结肠癌模型中均观察到oHSV2的抗肿瘤功效。oHSV2有效消除肿瘤并延长小鼠生存期且无副作用。此外，oHSV2治疗有效预防了再次接种肿瘤和远处植入肿瘤的生长。脾脏免疫细胞对肿瘤细胞的特异性杀伤能力增强。oHSV2治疗有效降低了脾脏中抑制性免疫细胞（调节性T细胞[Tregs]和髓源性抑制细胞[MDSCs]）的含量，并增加了阳性免疫细胞（自然杀伤细胞[NK]、CD8 T细胞和树突状细胞[DCs]）的含量。此外，oHSV2治疗重塑了肿瘤免疫微环境。总之，oHSV2治疗可有效消除原发性肿瘤，产生肿瘤特异性免疫，并引发免疫记忆以抑制肿瘤复发和转移。此外，这种病毒疗法可重塑小鼠脾脏和肿瘤微环境的免疫状态，从而进一步提高抗肿瘤治疗效果。
