OncoTargets and Therapy (Feb 2020)
Embelin Promotes Oncolytic Vaccinia Virus-Mediated Antitumor Immunity Through Disruption of IL-6/STAT3 Signaling in Lymphoma
Abstract
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 [email protected] 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 [email protected]: 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
