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

Abstract

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.

Establishment of Immune-related Gene Pair Signature to Predict Lung Adenocarcinoma Prognosis

“…TME has crucial effects on the initiation, development, metastasis, and recurrence of carcinoma 4,5 . As the essential ingredients of TME, immune and stromal cells play substantial roles in signal transduction, immune surveillance, immune escape, and patient prognosis 6,7 . For instance, the activation of CD8+ T cells, which are the important components of immune cells, could improve the survival in gastric cancer mouse models 8 .…”

Intratumoral OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: a multicenter, phase I/II clinical trial

“…6 8 Moreover, a specific antitumor immune response and a long-term effect to inhibit tumor recurrence and metastasis were observed in a murine colon cancer model treated with OH2. 9 These data validated subsequent clinical investigation of the drug.…”

In Situ Cancer Vaccination and Immunovirotherapy Using Oncolytic HSV

“…Once the OV or oHSV arrives at the tumor, infection results in immunogenic cell death, as well as the release or exposure of viral antigens or pathogen-associated molecular patterns (PAMPs) and tumor-associated antigens (TAAs), including neoantigens and danger-associated molecular patterns (DAMPs), such as ATP, HMGB1, calreticulin, and an inflammatory response [ 14 , 15 , 16 ]. This in turn sends pro-inflammatory signals, which recruit NK cells and professional antigen-presenting cells (APCs), mostly dendritic cells (DCs) and macrophages to the infection site, ultimately priming and activating tumor-specific T cells [ 17 , 18 , 19 ]. The activated T cells proliferate and travel to the TME and exert their effector functions against cancer cells ( Figure 2 ).…”

“…This anti-tumor activity was associated with an elevation of NK cells and a mild decrease of Tregs in the spleen [ 42 ]. oHSV2 was efficacious against a treated subcutaneous CT26 tumor and demonstrated a systemic immune response against non-injected tumors, which was associated with increased NK, CD8 + T, and dendritic cells in the tumor [ 19 ]. Us3 of HSV-2 and HSV-1 have many similar functions and one of them is prevention of apoptosis.…”