Molecular Therapy - Oncolytics
Volume 16, 27 March 2020, Pages 158-171
Journal home page for Molecular Therapy - Oncolytics

Original Article
oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

https://doi.org/10.1016/j.omto.2019.12.012Get rights and content
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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.

Keywords

oncolytic virus
oHSV2
colon carcinoma
tumor microenvironment
immune status
tumor-specific immune response

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These authors have contributed equally to this work