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

Abstract

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.

Predictive therapeutic planning for irreversible electroporation treatment of spontaneous malignant glioma

“…55,56 Despite promising results, there are limited studies evaluating the IRE-induced immune response and there is a need for additional studies that include combinatorial therapies as well. 57 The limitations of the current study lie in the heterogeneity of the patient population and the tumor types and locations. The seven patients are from different types of dog breeds which means a large variability in the genetic factors and possibly differences in the capabilities of the immune system.…”

“…Specifically, recent IRE studies suggest that there might be an immune response that is triggered with the nonthermal ablation and may help in tumor control . Despite promising results, there are limited studies evaluating the IRE‐induced immune response and there is a need for additional studies that include combinatorial therapies as well …”

Electrical Membrane Breakdown (EMB): Preliminary Findings of a New Method of Non-thermal Tissue Ablation

“…The four requirements for activation of the acquired immune system are antigen presentation, antigen recognition by T-cells, interaction of costimulatory molecules, and the presence of danger signals [10] and the method of ablation likely influences these factors. For example, protein denaturation by ablation may interfere with antigen presentation or recognition.…”

Thermal Ablation of Lung Tumors: Focus on Microwave Ablation

“…The heat also has an immunomodulatory effect by releasing intact antigens that can trigger an antitumor immune response [97,98]. Therefore, the size of the ablation zone can be enhanced by the concomitant local application of cytotoxic drugs [95,99].…”