**5. Conclusions**

Although the OVT is not a new concept in cancer, the concerns of possible adverse events and unspecific infection hamper enough development in this era. The emerging genetic manipulations of OVs facilitate clinical studies with much lower concerns and reintroduce OVT as a promising immunotherapeutic approach. However, many questions should still be addressed. Finding the appropriate OV for each tumor, the best combination therapy, higher OVT efficacy and safety, and optimal delivery system require further knowledge about the cellular and molecular interaction between the OVs and the cells present in the TME. The results of current clinical trials could pave the way for OVT in the clinic.

**Author Contributions:** X.-Z.M. and J.-X.S.: Conception, design and inviting co-authors to participate. K.-T.J., W.-L.D., Y.-Y.L. and H.-R.L.: Writing original manuscript draft. X.-Z.M. and J.-X.S.: Review and editing of manuscript critically for important intellectual content and provided comments and feedback for the scientific contents of the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** This work was supported by Zhejiang Provincial Science and Technology Projects (No. LGD19H160001 to K.-T.J.), Zhejiang Provincial Natural Science Foundation of China (No. LY21H160048 to J.-X.S.), National Natural Science Foundation of China (No. 81672430 to X.-Z.M.).

**Conflicts of Interest:** The authors declare no conflict of interest.
