| Summary: | Peng Wang,1 Yi Wu,2 Chen Yang,3 Guanan Zhao,4 Yonghua Liu,5 Gang Cheng,6 Shibing Wang7,8 1Medical Laboratory Center, Lishui City People’s Hospital, Lishui, People’s Republic of China; 2Department of Hematology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Department of Clinical Medicine, Qingdao University, Qingdao, People’s Republic of China; 4Department of General Surgery, Lishui City People’s Hospital, Lishui, People’s Republic of China; 5Department of Hematology, Lishui City People’s Hospital, Lishui, People’s Republic of China; 6Department of Stomatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 7Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 8Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of ChinaCorrespondence: Gang ChengDepartment of Stomatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, People’s Republic of ChinaEmail 3067406217@qq.comShibing WangClinical Research Institute, Zhejiang Provincial People’s Hospital People’s Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, People’s Republic of ChinaTel/Fax +86-571-85893781Email wangshibing@hmc.edu.cnObjective: Oncolytic virotherapy is a promising alternative to conventional treatment, yet limited viral replication and immune-negative feedback are the major hurdles to effective viro-immunotherapy.Methods: In this study, we found that use of an adjuvant of embelin, a small molecular inhibitor of XIAP, increased the replication of oncolytic vaccinia virus (OVV) by mitigating antiviral innate immunity. Moreover, embelin suppresses constitutive STAT3 phosphorylation and mitigates OVV-induced activation of STAT3 in lymphoma. In the subcutaneous lymphoma model, embelin significantly enhanced the therapeutic efficacy of OVV and prolonged the survival. In addition, embelin significantly increased the OVV-induced infiltration of T cells and NK cells and decreased the number of OVV-induced myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment.Results: Our results explored the ability of OVV and embelin in combination to enhance lymphoma cell lysis, revealing a beneficial combinatorial effect wherein both lymphoma cell lysis and OVV replication were enhanced both in vitro and in an in vivo murine model system.Conclusion: Our findings indicate the utility of embelin as an adjuvant for oncolytic viro-immunotherapy.Keywords: oncolytic vaccinia virus, embelin, IL-6/STAT3, immunotherapy, lymphoma
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