重组人5型腺病毒（H101）是一种用于治疗鼻咽癌的溶瘤病毒。由于E1B-55kD和E3区域的缺失，H101被认为可以选择性抑制鼻咽癌。 H101 是否通过不同机制抑制其他类型的肿瘤仍不清楚。在这项研究中，我们研究了 H101 对黑色素瘤的影响。我们建立了B16F10黑色素瘤异种移植小鼠模型，并通过瘤内注射H101（1 × 108 TCID50）连续5天治疗小鼠。我们发现 H101 治疗显着抑制小鼠 B16F10 黑色素瘤的生长。 H101处理显着增加了CD8 T细胞的浸润并减少了M2型巨噬细胞的比例。我们证明 H101 对 B16F10 细胞表现出低细胞毒性，但内皮细胞对 H101 处理更敏感。 H101 以 caspase-1/GSDMD 依赖性方式诱导内皮细胞焦亡。此外，我们还发现，H101与免疫检查点抑制剂PD-L1抗体（10mg/kg，腹膜内注射，每三天一次，共3次）联合使用对小鼠B16F10肿瘤生长具有协同抑制作用。这项研究表明，除了溶瘤作用外，H101还通过促进抗肿瘤免疫和诱导血管内皮细胞焦亡来抑制黑色素瘤生长。© 2024。作者，经中国科学院上海药物研究所独家许可科学与中国药理学会.

Recombinant human type 5 adenovirus (H101) is an oncolytic virus used to treat nasopharyngeal carcinoma. Owing to the deletion of the E1B-55kD and E3 regions, H101 is believed to selectively inhibit nasopharyngeal carcinoma. Whether H101 inhibits other type of tumors via different mechanisms remains unclear. In this study we investigated the effects of H101 on melanomas. We established B16F10 melanoma xenograft mouse model, and treated the mice with H101 (1 × 108 TCID50) via intratumoral injection for five consecutive days. We found that H101 treatment significantly inhibited B16F10 melanoma growth in the mice. H101 treatment significantly increased the infiltration of CD8+ T cells and reduced the proportion of M2-type macrophages. We demonstrated that H101 exhibited low cytotoxicity against B16F10 cells, but the endothelial cells were more sensitive to H101 treatment. H101 induced endothelial cell pyroptosis in a caspase-1/GSDMD-dependent manner. Furthermore, we showed that the combination of H101 with the immune checkpoint inhibitor PD-L1 antibody (10 mg/kg, i.p., every three days for three times) exerted synergic suppression on B16F10 tumor growth in the mice. This study demonstrates that, in addition to oncolysis, H101 inhibits melanoma growth by promoting anti-tumor immunity and inducing pyroptosis of vascular endothelial cells.© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.