Combined radiotherapy and immune checkpoint inhibition for the treatment of advanced hepatocellular carcinoma

Shannon, Alexander H.; Manne, Ashish; Pardo, D.A. Diaz; Pawlik, Timothy M.

doi:10.3389/fonc.2023.1193762

Cited by 3 publications

(3 citation statements)

References 134 publications

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“…Major inhibitors relating these immunoreceptors, in the format of monoclonal antibodies, include PD-1 inhibitors nivolumab, pembrolizumab and sintilimab, PD-L1 inhibitor atezolizumab and durvalumab, and CTLA-4 blocker tremelimumab and ipilimumab, etc. ( Li et al, 2023a ; Shannon et al, 2023 ).…”

Section: Time and Targeted Therapies In Hccmentioning

confidence: 99%

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

Wang,

Liu,

et al. 2024

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% of primary liver cancer. The advent of immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized the treatment of HCC in late-stage and unresectable HCC, as ICIs alone were disappointing in treating HCC. In addition to the altered immune microenvironment, abnormal lipid metabolism in the liver has been extensively characterized in various types of HCC. Stains are known for their cholesterol-lowering properties and their long history of treating hypercholesterolemia and reducing cardiovascular disease risk. Apart from ICI and other conventional therapies, statins are frequently used by advanced HCC patients with dyslipidemia, which is often marked by the abnormal accumulation of cholesterol and fatty acids in the liver. Supported by a body of preclinical and clinical studies, statins may unexpectedly enhance the efficacy of ICI therapy in HCC patients through the regulation of inflammatory responses and the immune microenvironment. This review discusses the abnormal changes in lipid metabolism in HCC, summarizes the clinical evidence and benefits of stain use in HCC, and prospects the possible mechanistic actions of statins in transforming the immune microenvironment in HCC when combined with immunotherapies. Consequently, the use of statin therapy may emerge as a novel and valuable adjuvant for immunotherapies in HCC.

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Section: Time and Targeted Therapies In Hccmentioning

confidence: 99%

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

Wang,

Liu,

et al. 2024

Front. Pharmacol.

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“…The results, however, are quite limited, and refinement of the procedures is warranted [ 21 ]. In clinical trials with HCC patients, it was observed that the addition of RT helps to augment the effects of ICI [ 22 ]. Combination of thermal ablation may also be combined with CPI, and ongoing clinical trials were reported [ 23 ] Adoptive cellular therapy (ACT) is based on the patient’s immune cells, which are manipulated and then reinfused back into the patient.…”

Section: Enforcement Of Anti-tumor Immunity By Immunomanipulationmentioning

confidence: 99%

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

Keisari,

Kelson

2023

Cancer Metastasis Rev

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“…The favorable effects of radiotherapy deliver a rationale for the combined therapeutic strategy. Application of complex treatment methods, including the use of radiotherapy as an activator of internal anti-cancer mechanisms in support of chemotherapy and immunotherapy, is recommended ( Zhang et al, 2023b ; Pontoriero et al, 2023 ; Shannon et al, 2023 ; Viswanath et al, 2023 ). In this study, we discuss the role of radiotherapy in the regulation of TME-related cancer-promoting effects.…”

Section: Introductionmentioning

confidence: 99%

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

Zhao,

Mo,

Neganova

et al. 2023

Front. Cell Dev. Biol.

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Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one of the crucial components of the cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research is focused on the identification of methods that should increase cancer cell sensitivity to radiation and activate anti-cancer immunity mechanisms. Radiation treatment activates various cells of the tumor microenvironment (TME) and impacts tumor growth, angiogenesis, and anti-cancer immunity. Radiotherapy was shown to regulate signaling and anti-cancer functions of various TME immune and vasculature cell components, including tumor-associated macrophages, dendritic cells, endothelial cells, cancer-associated fibroblasts (CAFs), natural killers, and other T cell subsets. Dual effects of radiation, including metastasis-promoting effects and activation of oxidative stress, have been detected, suggesting that radiotherapy triggers heterogeneous targets. In this review, we critically discuss the activation of TME and angiogenesis during radiotherapy which is used to strengthen the effects of novel immunotherapy. Intracellular, genetic, and epigenetic mechanisms of signaling and clinical manipulations of immune responses and oxidative stress by radiotherapy are accented. Current findings indicate that radiotherapy should be considered as a supporting instrument for immunotherapy to limit the cancer-promoting effects of TME. To increase cancer-free survival rates, it is recommended to combine personalized radiation therapy methods with TME-targeting drugs, including immune checkpoint inhibitors.

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Combined radiotherapy and immune checkpoint inhibition for the treatment of advanced hepatocellular carcinoma

Cited by 3 publications

References 134 publications

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

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

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

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