Abstract
Simple SummaryInterventional radiology image-guided locoregional therapies for the treatment of HCC have demonstrated to be characterized by immunomodulatory effects on the tumoral microenvironment, and, possibly, systemic. Immunotherapy has gained an important role in the treatment of HCC over the last several years. Currently, there is great interest in combining locoregional therapies with immunotherapy, as this could open a new chapter in the history of HCC treatment. In this review, after describing the immune system changes caused by the tumor, we describe, for each locoregional therapy, technique and immunomodulatory effects. Then, we describe the current status of immunotherapy in HCC and report the ongoing clinical studies testing the combination treatment.Image-guided locoregional therapies (LRTs) are a crucial asset in the treatment of hepatocellular carcinoma (HCC), which has proven to be characterized by an impaired antitumor immune status. LRTs not only directly destroy tumor cells but also have an immunomodulating role, altering the tumor microenvironment with potential systemic effects. Nevertheless, the immune activation against HCC induced by LRTs is not strong enough on its own to generate a systemic significant antitumor response, and it is incapable of preventing tumor recurrence. Currently, there is great interest in the possibility of combining LRTs with immunotherapy for HCC, as this combination may result in a mutually beneficial and synergistic relationship. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of LRTs, reducing recurrence cases and improving outcome. On the other hand, LTRs counteract the typical immunosuppressive HCC microenvironment and status and could therefore enhance the efficacy of immunotherapy. Here, after reviewing the current therapeutic options for HCC, we focus on LRTs, describing for each of them the technique and data on its effect on the immune system. Then, we describe the current status of immunotherapy and finally report the recently published and ongoing clinical studies testing this combination.
Highlights
Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; Gastroenterology Department, IRCCS Cà Granda Fondazione Ospedale Maggiore Policlinico, Radiology Department, IEO European Institute of Oncology IRCCS, 20122 Milan, Italy; Diagnostic and Interventional Radiology Department, ASST Santi Paolo e Carlo, 20122 Milan, Italy; Simple Summary: Interventional radiology image-guided locoregional therapies for the treatment of hepatocellular carcinoma (HCC) have demonstrated to be characterized by immunomodulatory effects on the tumoral microenvironment, and, possibly, systemic
The impressive benefit provided by immunotherapy leads to the question if there is a rationale to support the combination of surgery or locoregional therapies (LRTs) for early or intermediate HCC with immunotherapy, given the established effect of this therapy and its modest side effects, with the possibility of shifting immunotherapy from an advanced treatment setting to an adjuvant setting, considering that it does not require hepatic metabolism and that HCC is regarded as an immunogenic cancer [12]
LRTs have the potential of shaping tumor immunity by altering the composition of the HCC microenvironment; in particular, they lead to the release from dying tumor cells of cryptic tumor-associated antigens (TAAs) and tumor neoantigens that become accessible to the immune system, acting as novel targets for antigen-presenting cells (APCs), mainly dendritic cells (DCs)
Summary
Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide, after lung and colorectal cancer. Many studies have tested the ability to improve survival combining the abovementioned treatments as well as neoadjuvant or adjuvant therapies All these approaches have failed to improve overall survival (OS), so that none of them are recommended by the Scientific Societies. The impressive benefit provided by immunotherapy leads to the question if there is a rationale to support the combination of surgery or LRTs for early or intermediate HCC with immunotherapy, given the established effect of this therapy and its modest side effects, with the possibility of shifting immunotherapy from an advanced treatment setting to an adjuvant setting, considering that it does not require hepatic metabolism and that HCC is regarded as an immunogenic cancer [12]. We review the rationale supporting the combination of immunotherapy with LRTs and summarize the recently published and ongoing clinical studies testing this combination
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