Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells  

作　　者：Zhi-ming Wang Meng-kai Li Qing-ling Yang Shi-xin Duan Xin-yi Lou Xin-yi Yang Ying Liu Yu-wen Zhong Yu Qiao Zi-shu Wang Lei Sun Feng Qian 

机构地区：[1]Shanghai Frontiers Science Center of Drug Target Identification and Delivery [2]Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,School of Pharmaceutical Sciences [3]National Key Laboratory of Innovative Immunotherapy,Shanghai Jiao Tong University,Shanghai 200240,China [4]Anhui Province Key Laboratory of Cancer Translational Medicine,Bengbu Medical University,Bengbu 233030,China [5]Department of Medical Oncology,Anhui Province Key Laboratory of Translational Cancer Research,First Affiliated Hospital of Bengbu Medical College,Bengbu Medical University,Bengbu 233004,China

出　　处：《Acta Pharmacologica Sinica》2024年第12期2646-2656,共11页中国药理学报（英文版）

基　　金：supported by National Key Research and Development Program of China(2023YFA0913700);National Natural Science Foundation of China(82073858,82173821,82273934,and 82373875);Natural Science Foundation of Shanghai(21ZR1432700);the open project of Anhui Province Key Laboratory of Translational Acta Pharmacologica Sinica(2024)45:2646-2656 Cancer Research(KFKT202302);Anhui Province Scientific Research Compilation Plan Project(2022AH040214);Anhui Province Translational Special Project for Clinical Medical Research(202204295107020038);Shanghai Society of Biotechnology(SSBT);Key Research and Development Projects in Anhui Province for A(202104j07020021)。

摘　　要：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.

关 键 词：oncolytic viruses H101 MELANOMA endothelial cells PYROPTOSIS PD-L1 antibody 

分 类 号：R730.3[医药卫生—肿瘤]