Suppression of multiple mouse models of refractory malignancies by reprogramming IL-18 ligand-receptor interaction

• Published in: Nature communications Vol. 16; no. 1; pp. 6136 - 18
• Main Authors: Fan, Zhen, Liu, Ying, Lin, Xueying, Zhang, Jifu, Chen, Jiehong, Yi, Shiming, Hu, Cheng, Liu, Xincheng, Guo, Cui, Xu, Cuiying, Chen, Xiaoyu, Tian, Xuyan, Liang, Xuanming, Liu, Yang, Hu, Linyi, Huang, Shanyu, Guo, Li, Zhu, Wenbo, Hu, Jun, Yan, Guangmei, Lin, Yuan, Cai, Jing, Liang, Jiankai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.07.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/127/1213; 631/250/580/1884/2323; 631/326/596/2561; 631/67/1059/2325; 631/67/327; 96; 96/21; 96/31; 96/47; 96/63; 96/95; Animal models; Animals; Anticancer properties; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell differentiation; Cell Line, Tumor; Chemokines; Cytokines; Dendritic cells; Dendritic Cells - immunology; Disease Models, Animal; Effectiveness; FDA approval; Feedback loops; Female; Humanities and Social Sciences; Humans; Immune checkpoint inhibitors; Immunological memory; Immunology; Immunotherapy; Infections; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Interferon-gamma - metabolism; Interleukin 18; Interleukin 18 receptors; Interleukin-18 - genetics; Interleukin-18 - immunology; Interleukin-18 - metabolism; Intravenous administration; Ligands; Lymphocytes; Lymphocytes T; Malignancy; Melanoma; Metastases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; multidisciplinary; Neoplasms - immunology; Neoplasms - therapy; Oncolysis; Oncolytic Virotherapy - methods; Oncolytic Viruses - genetics; PD-L1 protein; Positive feedback; Proteins; Receptors; Receptors, Interleukin-18 - genetics; Receptors, Interleukin-18 - metabolism; Science; Science (multidisciplinary); Solid tumors; Tumor microenvironment; Tumor Microenvironment - immunology; Tumors; Viruses; γ-Interferon

Achieving a cure is an urgent need for patients with advanced solid tumors. Here, we discover that oncolytic virus (OV) infection enhances IL-18 receptor expression but fails to increase IL-18 ligand expression. Therefore, we engineer armed oncolytic alphavirus M1 expressing wild-type IL-18 (wtIL-18...