Harnessing the immunomodulatory effect of thermal and non-thermal ablative therapies for cancer treatment

Minimally invasive interventional therapies are evolving rapidly and their use for the treatment of solid tumours is becoming more extensive. The in situ destruction of solid tumours by such therapies is thought to release antigens that can prime an antitumour immune response. In this review, we offer an overview of the current evidence for immune response activation associated with the utilisation of the main thermal and non-thermal ablation therapies currently in use today. This is followed by an assessment of the hypothesised mechanisms behind this immune response priming and by a discussion of potential methods of harnessing this specific response, which may subsequently be applicable in the treatment of cancer patients. References were identified through searches of PubMed/MEDLINE and Cochrane databases to identify peer-reviewed original articles, meta-analyses and reviews. Papers were searched from 1850 until October 2014. Articles were also identified through searches of the authors' files. Only papers published in English were reviewed. Thermal and non-thermal therapies have the potential to stimulate antitumour immunity although the current body of evidence is based mostly on murine trials or small-scale phase 1 human trials. The evidence for this immune-modulatory response is currently the strongest in relation to cryotherapy and radiotherapy, although data is accumulating for related ablative treatments such as high-intensity focused ultrasound, radiofrequency ablation and irreversible electroporation. This effect may be greatly enhanced by combining these therapies with other immunostimulatory interventions. Evidence is emerging into the immunomodulatory effect associated with thermal and non-thermal ablative therapies used in cancer treatment in addition to the mechanism behind this effect and how it may be harnessed for therapeutic use. A potential exists for treatment approaches that combine ablation of the primary tumour with control and possible eradication of persistent, locally recurrent and metastatic disease. However, more work is needed into each of these modalities, initially in further animal studies and then subsequently in large-scale prospective human studies.