Oncolysis without viruses — inducing systemic anticancer immune responses with local therapies

Local administration of oncolytic viruses to tumours can promote anticancer immune responses that lead to the abscopal regression of distant metastases, especially in patients receiving systemic immune-checkpoint inhibitors. Growing preclinical evidence indicates that non-virally induced oncolysis, defined as chemical or physical treatment administered locally to destroy malignant lesions, can promote a similar effect owing to the release of danger-associated molecular patterns that lead to the recruitment of immune cells, thus inducing a systemic response against tumour antigens that protects against local disease relapse and also mediates distant antineoplastic effects. An accumulating body of preclinical evidence supports the implementation of therapies that combine oncolysis with local or systemic immunotherapies. In this Review, we summarize the available data on innovative non-viral oncolysis strategies, including intratumorally applied cytotoxicants, photodynamic therapy, laser therapy, microwave, radiofrequency or photothermal ablation, high-intensity focused ultrasonography and cryotherapy for the local treatment of patients with solid tumours. Oncolytic viruses are beginning to enter clinical use in patients with cancer despite regulatory and practical considerations precluding the widespread use of such therapies. Here, the authors describe the potential of non-viral methods in achieving oncolytic effects and how these effects might prime the development of antitumour immune responses in patients with cancer.