Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?

Figure 1

Thermal ablation and the proposed mechanisms for immunostimulation and oncogenesis in the liver. In the central heating zone, temperatures > 50°C cause coagulation necrosis. In the adjacent peripheral heating zone, lethal hyperthermia temperatures may not be achieved, leading to either necrosis, apoptosis, or recovery. In this zone, hyperemia results in increased oxygen delivery, and cell death results in the release of cytokines and other immune stimulatory factors such as heat-shock protein 70 (HSP70). As a result, either immunostimulation due to T-cell activation or immunosuppression due to T-cell anergy in the setting of apoptosis may occur. Sublethal thermal injury to the adjacent hepatocytes causes the release of additional growth factors such as c-Met that can cause systemic tumor growth stimulation.