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oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity.
Molecular Therapy: Oncology ( IF 5.3 ) Pub Date : 2020-01-11 , DOI: 10.1016/j.omto.2019.12.012
Wen Zhang 1 , Xiao Hu 2 , Jing Liang 3 , Yujie Zhu 2 , Beibei Zeng 3 , Lin Feng 2 , Changyun Zhao 4 , Shangmei Liu 3 , Binlei Liu 5 , Kaitai Zhang 2
Affiliation  

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 in vivo 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.



中文翻译:

oHSV2可以通过改变肿瘤微环境的免疫状态并诱导抗肿瘤免疫来靶向鼠结肠癌。

溶瘤病毒是有前途的免疫试剂。大量研究表明溶瘤病毒疗法对许多肿瘤有效。本文中,我们研究了溶瘤性2型单纯疱疹病毒oHSV2对小鼠结肠癌的治疗作用。在体内在单侧和双侧结肠癌模型中均观察到了oHSV2的抗肿瘤功效。oHSV2有效消除了肿瘤,延长了小鼠的生存期,且没有副作用。另外,用oHSV2治疗有效地防止了再发肿瘤和远处植入的肿瘤的生长。增强了脾脏免疫细胞对肿瘤细胞的特异性杀伤能力。oHSV2治疗可有效降低抑制性免疫细胞(调节性T细胞[Tregs]和髓样来源的抑制性细胞[MDSCs])的含量,并增加阳性免疫细胞(天然杀伤性[NK],CD8 +T和脾脏中的树突状细胞[DCs]。此外,用oHSV2进行的治疗重塑了肿瘤免疫微环境。总之,用oHSV2进行治疗可以有效消除原发性肿瘤,产生肿瘤特异性免疫力,并引发免疫记忆,从而抑制肿瘤的复发和转移。此外,这种病毒疗法可以改变小鼠脾脏和肿瘤微环境的免疫状态,从而可以进一步提高治疗性抗肿瘤作用。

更新日期:2020-01-11
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