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Life sciences · Journal article
Frontiers in Immunology · September 30, 2026
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Background Intraperitoneal metastasis is a frequent progression in colon cancer, highlighting the critical need for enhanced therapeutic approaches. Oncolytic virus (OV) therapy has emerged as a promising immunotherapeutic strategy. The combination of OVs with immune checkpoint inhibitors (ICIs) has demonstrated an enhanced anti-tumor response. Methods We generated the intraperitoneal-subcutaneous bilateral colon cancer xenograft model to simulate intraperitoneal metastatic colon cancer, and evaluated the systemic antitumor efficacy of the oncolytic HSV-1 virus VT1092M in combination with ICIs (anti-PD-L1 antibody and anti-CTLA-4 antibody). Results and discussion Intraperitoneal administration of VT1092M markedly suppressed intraperitoneal cancer progression and enhanced the superior antitumor efficacy of ICIs immunotherapy in murine intraperitoneal metastatic colon cancer. Notably, treatment of VT1092M combined with anti-CTLA-4 antibody could eliminate both intraperitoneal metastases and subcutaneous tumors, while also inhibiting the formation of peritoneal blood vessels and malignant ascites. The synergistic combination of VT1092M and anti-CTLA-4 elicited potent intraperitoneal and systemic antitumor immunity, culminating in durable, tumor-specific memory that significantly prolonged survival in mice with colorectal intraperitoneal metastases compared to either monotherapy. Mechanistically, the combination therapy activates the anti-tumor immune environment within the peritoneal cavity, leading to a significant increase in tumoricidal CD8 + T cells and M1 macrophages, as well as the reprogramming of transcriptional signatures associated with the tumor immune response within the tumor microenvironment. Ultimately, intraperitoneal immunotherapy with VT1092M enhances the efficacy of immune checkpoint blockade in suppressing intraperitoneal metastatic colorectal cancer and induces durable tumor-specific immune memory, thereby exerting substantial anti-tumor effects. This finding highlights the potential of synergistically combining oncolytic viruses with ICIs to advance immunotherapeutic strategies for intraperitoneal metastatic colorectal cancer.