Immuno-thermal ablations - boosting the anticancer immune response

Abstract

The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades.

Keywords: Checkpoint inhibition; Combination Therapy; Cryoablation; Microwave ablation; Radiofrequency ablation.

Fig. 1

a Indirect ablative damage triggers apoptotic cell death and does not induce co-stimulator expression on DCs. In contrast, direct ablative damage releases DAMPs that activate the NF-κβ pathway and induce co-stimulator expression in DCs, thereby promoting the activation and proliferation of T cells [2, 3, 7, 12, 13]. b Legend for Figs. 1 and 2

Fig. 2

a Ablation therapy alone is often sufficient to activate the immune system; however, the CTLA-4 and PD-1 checkpoints regulate and inhibit the induction of a more robust immune response [2, 3, 7, 12, 13]. B - Both anti -PD-1 and anti-CTLA-4 antibodies enhance the immune response induced via ablation monotherapy by blocking regulatory checkpoints. [, , , –14, 35, 54]