Thermal ablation and immunotherapy for hepatocellular carcinoma: Recent advances and future directions

Abstract

Hepatocellular carcinoma (HCC) is one of most common cancers that cause death in the world. Thermal ablation (TA) is an important alternative treatment method for HCC patients who are not appropriate for surgery or liver transplantation. Particularly for small and early HCCs, TA can be considered as the first-line curative treatment. However, local and distant recurrence rates are still high even though the TA equipment and technology develop rapidly. Immunotherapy is a novel systemic treatment method to enhance the anti-tumor immune response of HCC patients, which has the potential to reduce the tumor recurrence and metastasis. The combination of local TA and systemic immunotherapy for HCCs may be an ideal treatment for enhancing the efficacy of TA and controlling the recurrence. Herein we summarize the latest progress in TA, immunotherapy, and their combination for the treatment of patients with HCC and discuss the limitations and future research directions of the combined therapy.

Present and future of metal nanoparticles in tumor ablation therapy

“…76,217,218,253 Although various ablation techniques have their unique advantages in the field of tumor treatment, they also face great challenges and dilemmas. 219,220 Firstly, almost all current tumor ablation techniques have the problem of residual tumor due to incomplete ablation, thus the problem of residual tumor after ablation, and consequently tumor recurrence and distant metastasis has become an urgent clinical problem. Secondly, as tumor ablation is a localised treatment, systemic treatment is not possible for patients with tumors.…”

High Expression of TGF-β1 Contributes to Hepatocellular Carcinoma Prognosis via Regulating Tumor Immunity

“…Immunotherapy is a novel systemic treatment approach for enhancement of the anti-tumor immune response of HCC patients, which has the potential to reduce tumor recurrence and metastasis ( 27 ). TGF-β signaling can promote tumor progression through immunosuppression ( 6 , 28 – 30 ), while TGF-β1 can directly suppress immunosurveillance by inhibiting the anti-tumor activity of infiltrating immune cells and subsequently facilitating the recruitment and sustenance of pro-tumoral immune cells to enhance metastatic progression ( 20 ).…”

Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis

“…These elicit a certain degree of anti-tumor immune response as an in situ vaccine, but the response is too weak to effectively inhibit tumor progression ( 10 , 42 – 45 ). Combined immunotherapy, on the basis of local ablation therapy, is an ideal method to enhance the efficacy of thermal ablation therapy ( 10 , 23 , 46 ). As a novel immunomodulatory agent, R848 has attracted widespread attention in recent years, which plays an important role in promoting the activation of NK cell and CD8 + T cell as well as the release of proinflammatory cytokines, such as IFN-α, IL-2, IL-6, and TNF-α ( 27 , 47 – 49 ).…”

“…Clinical trials of thermal ablation combined with immunotherapy, such as anti-PD1/anti-PDL1/anti-CTLA4 antibody, in the treatment of liver cancer have been widely carried out. Patients who received combination therapy had different degrees of improvement in overall survival or progression-free survival ( 23 ).…”