Combination of natural killer cell-based immunotherapy and irreversible electroporation for the treatment of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is among the most lethal cancer types despite great advancement in overall survival of the patients over the last decades. Surgical resection or partial hepatectomy has been approved as the curative treatment for early-stage HCC patients however only up to 30% of them are eligible for the procedures. Natural killer (NK) cells are cytotoxic lymphocytes recognized for killing virally infected cells and improving immune functions for defending the body against malignant cells. Although autologous NK cells failed to demonstrate significant clinical benefit, transfer of allogeneic adoptive NK cells arises as a promising approach for the treatment of solid tumors. The immunosuppressive tumor microenvironment and inadequate homing efficiency of NK cells to tumors can inhibit adoptive transfer immunotherapy (ATI) efficacy. However, potential of the NK cells is challenged by the transfection efficiency. The local ablation techniques that employ thermal or chemical energy have been investigated for the destruction of solid tumors for three decades and demonstrated promising benefits for individuals not eligible for surgical resection or partial hepatectomy. Irreversible electroporation (IRE) is one of the most recent minimally invasive ablation methods that destruct the cell within the targeted region through non-thermal energy. IRE destroys the tumor cell membrane by delivering high-frequency electrical energy in short pulses and overcomes tumor immunosuppression. The previous studies demonstrated that IRE can induce immune changes which can facilitate activation of specific immune responses and improve transfection efficiency. In this review paper, we have discussed the mechanism of NK cell immunotherapy and IRE ablation methods for the treatment of HCC patients and the combinatorial benefits of NK cell immunotherapy and IRE ablation.

Tumor ablation induced anti-tumor immunity: destruction of the tumor in situ with the aim to evoke a robust anti-tumor immune response

“…CARs recognize surface proteins typically through an antibody-derived scFv recognition domain Although ablation in combination with ACT is a promising approach, it did not yield yet sufficient promising results [ 20 ]. Recent studies have demonstrated that a combination of irreversible electroporation (IRE) and NK cell-based immunotherapy has the potential to improve patient survival in the advanced-stage liver and pancreatic cancers [ 24 ].…”

What Inhibits Natural Killers’ Performance in Tumour

“…IRE is a non-invasive and non-thermal ablation technique that allows the destruction of the tumour microenvironment with minimal damage to associated tissue. Such a method, in combination with NK cell adoptive transfer, increased the number of patients responding to therapy from 68.2% to 88.9% [219].…”

A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of hepatocellular carcinoma

“…In recent years, percutaneous local ablation has been recognized as a potential treatment for small hepatocellular carcinoma (typically < 3-4 cm), supplemented by surgical resection and liver transplantation 4 . The commonly used ablation methods for HCC are thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation 5 . The goal of thermal ablation is to induce tumor coagulative necrosis at temperatures above 60°C or below − 40°C 6 .…”