Autophagy in Tumor Immunity and Viral-Based Immunotherapeutic Approaches in Cancer.

Ali Zahedi-Amiri,Behzad Yeganeh,Kyle Malone,Tommy Alain,Shawn T Beug

doi:10.3390/cells10102672

Ali Zahedi-Amiri, Behzad Yeganeh + Show 3 more

Open Access

https://doi.org/10.3390/cells10102672

Copy DOI

Abstract

Autophagy is a fundamental catabolic process essential for the maintenance of cellular and tissue homeostasis, as well as directly contributing to the control of invading pathogens. Unsurprisingly, this process becomes critical in supporting cellular dysregulation that occurs in cancer, particularly the tumor microenvironments and their immune cell infiltration, ultimately playing a role in responses to cancer therapies. Therefore, understanding “cancer autophagy” could help turn this cellular waste-management service into a powerful ally for specific therapeutics. For instance, numerous regulatory mechanisms of the autophagic machinery can contribute to the anti-tumor properties of oncolytic viruses (OVs), which comprise a diverse class of replication-competent viruses with potential as cancer immunotherapeutics. In that context, autophagy can either: promote OV anti-tumor effects by enhancing infectivity and replication, mediating oncolysis, and inducing autophagic and immunogenic cell death; or reduce OV cytotoxicity by providing survival cues to tumor cells. These properties make the catabolic process of autophagy an attractive target for therapeutic combinations looking to enhance the efficacy of OVs. In this article, we review the complicated role of autophagy in cancer initiation and development, its effect on modulating OVs and immunity, and we discuss recent progress and opportunities/challenges in targeting autophagy to enhance oncolytic viral immunotherapy.

Highlights

Oncolytic viruses (OVs), either occurring naturally or through genetic engineering, are promising candidate therapies against cancer since they can selectively amplify in and kill tumor cells without affecting normal cells
OVs can boost systemic anti-tumor immunity by lysing tumor cells; the consequent release of tumor-associated antigens (TAAs), damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs) to the tumor microenvironment (TME) promote activation of antigen-presenting cells (APCs), in turn stimulating anti-tumor adaptive immune responses [1,2]
ATG5 point mutations were detected in biopsies of patients with hepatocellular carcinoma, gastric and colorectal cancers, suggesting the potential involvement of ATG dysregulations in abnormal autophagy and tumor development [62]

Summary

Introduction

Oncolytic viruses (OVs), either occurring naturally or through genetic engineering, are promising candidate therapies against cancer since they can selectively amplify in and kill tumor cells without affecting normal cells. OVs can boost systemic anti-tumor immunity by lysing tumor cells; the consequent release of tumor-associated antigens (TAAs), damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs) to the tumor microenvironment (TME) promote activation of antigen-presenting cells (APCs), in turn stimulating anti-tumor adaptive immune responses [1,2]. With their unique capacity to encode for a vast array of therapeutic transgenes to enhance specific responses, OVs, represent promising candidate therapies against cancer. The prospect and challenges of combinatorial OV therapy with autophagy modulators in cancer immunotherapy are explored

Molecular Mechanism and Regulation of Autophagy

Autophagy in Tumor Initiation and Development

Autophagy in Tumor Immunity

Targeting Autophagy for Immunotherapy

Autophagy and OVs

Concluding Remarks and Future Perspectives