Objective: 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 phosphoryla-tion 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 infil-tration 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.
CITATION STYLE
Wang, P., Wu, Y., Yang, C., Zhao, G., Liu, Y., Cheng, G., & Wang, S. (2020). Embelin promotes oncolytic vaccinia virus-mediated antitumor immunity through disruption of IL-6/STAT3 signaling in lymphoma. OncoTargets and Therapy, 13, 1421–1429. https://doi.org/10.2147/OTT.S209312
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