Harnessing macrophages in thermal and non-thermal ablative therapies for urologic cancers - Potential for immunotherapy

Prostate and bladder cancers are one of the cancers occurring worldwide. In addition to radical surgery, the past decade has also focused on targeted therapy of overexpressed cancer proteins that are lethal and critical for cancer cell survival. However, targeted therapy cannot adapt for changing of cancer molecular characteristics and, ultimately, a clone that bypasses the targeted therapy emerges. This can be overcome by immunotherapy. New studies on ablative therapy of cancers show presence of immunomodulatory effect in these modalities. Tumor ablation prime the immune system for further destruction of persistent primary tumor in addition to destruction of concurrent metastatic disease and also reduce recurrence. Ablative therapies can achieve a state of increased antigenicity. Its combination with a novel macrophage targeted therapy may enhance immune priming, trafficking, and/or effector phases; thereby improving clinical outcomes. Tumor associated macrophages or M2 phenotype are now known to mediate this immunosuppressive pro-tumorigenic effect. Alteration of macrophage differentiation may enhance tumor destruction of ablative therapy. This breakthrough in immunotherapy opens up arenas for further robust clinical trials on combinatorial therapies. In the present review, we aim to elucidate the major aspects of immune stimulatory minimal invasive approaches by combining with macrophage directed pathways.