Targeting T Cell Subtypes for NAFLD and NAFLD-Related HCC Treatment: An Opinion

Zhang, Chunye; Yang, Ming

doi:10.3389/fmed.2021.789859

Cited by 13 publications

(9 citation statements)

References 73 publications

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“…18,19 In a preclinical model of NASH-induced HCC, immunotherapy against PD-1 amplified intratumorally activated CD8 + PD1+ T cells without leading to tumor regression. 20 This may be related to changes in subtype and function in the T cell population during the development of NAFLD-associated HCC. 21 Different stages of liver fibrosis and steatosis have different inflammatory microenvironments in the liver, and the interaction between PD-1/PD-L1 and adaptive immunity in the microenvironment maintains a fragile balance.…”

Section: Inflammatory Microenvironment and Immune Checkpoint Inhibito...mentioning

confidence: 99%

Inflammatory microenvironment and immunotherapy in hepatocellular carcinoma

Liu

2023

Eur J Inflamm

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Hepatocellular carcinoma (HCC) is considered a classic inflammation-associated tumor that usually originates from chronic hepatitis, where an intense and chronic inflammatory response leads to the accumulation of mutations and eventually carcinogenesis under conditions of persistent liver injury. In recent years, immunotherapy for HCC has continued to evolve, as the liver is naturally filled with a large variety of immune cells, making hepatocellular carcinoma a more complex inflammatory microenvironment unlike other tumors. With a better understanding of the specific inflammatory microenvironment of HCC, there is an opportunity to try new therapeutic strategies for HCC immunotherapy. In this paper, we review the immunotherapy of primary liver cancer in terms of the correlation between ICI drugs, ACT therapy and the inflammatory microenvironment of HCC, summarize and discuss the progress and difficulties of immunotherapy of liver cancer, and provide more scientific guidance for immunotherapy of primary liver cancer.

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Section: Inflammatory Microenvironment and Immune Checkpoint Inhibito...mentioning

confidence: 99%

Inflammatory microenvironment and immunotherapy in hepatocellular carcinoma

Liu

2023

Eur J Inflamm

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“…For example, the U.S. Food and Drug Administration approved the use of nivolumab (anti-PD1) or in combination with ipilimumab or ipilimumab (anti-CTLA-4) for the treatment of patients with HCC in certain conditions[ 9 - 11 ]. Furthermore, the state-art chimeric antigen receptor-engineered T-cell therapy has displayed the promise for HCC treatment[ 12 , 13 ].…”

Section: To the Editormentioning

confidence: 99%

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

Zhang¹,

Liu²,

Yang³

2022

WJGO

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third leading cause of cancer-related death worldwide. Factors including carcinogens, infection of hepatitis viruses, alcohol abuse, and metabolic disorders such as non-alcoholic fatty liver disease mainly contribute to HCC initiation and progression. Immunotherapy is one of the most powerful tools for unresectable HCC treatment in patients. CD8 + T cells are a major immune component in the tumor microenvironment with cytotoxic effects against cancer cells. However, these CD8 + T cells commonly display an exhaustion phenotype with high expression of programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing-3, and/or lymphocyte-activation gene 3, producing low levels of perforin (PRF1) and granzyme B (GZMB), as well as anti-tumor cytokines, such as interferon gamma and tumor necrosis factor alpha. In the referenced study, the authors also showed that deprivation of glutamine decreased the antitumor function of CD8 + T cells, as well as the production of PRF1 and GZMB. However, the role of each amino acid in T cell function and exhaustion may depend on tumor type and tumor microenvironment, including the source of other nutrients. Overall, amino acids or other nutrient metabolites in the tumor microenvironment play a pivotal role in both tumor growth and immune response.

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“…A recent study from this group also showed that loss of liver CD4 + T cells impaired immunotherapies such as RNA vaccine (M30) and anti-OX40 antibody-mediated treatment against tumor cell growth in the liver ( 42 ). Furthermore, there are several other subtypes of T cells play important roles in the NALFD or NAFLD-HCC pathogenesis ( 43 ).…”

Section: Obesity and Hccmentioning

confidence: 99%

Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options

2021

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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which will affect more than a million people by the year 2025. However, current treatment options have limited benefits. Nonalcoholic fatty liver disease (NAFLD) is the fastest growing factor that causes HCC in western countries, including the United States. In addition, NAFLD co-morbidities including obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) promote HCC development. Alteration of metabolites and inflammation in the tumor microenvironment plays a pivotal role in HCC progression. However, the underlying molecular mechanisms are still not totally clear. Herein, in this review, we explored the latest molecules that are involved in obesity, T2DM, and CVDs-mediated progression of HCC, as they share some common pathologic features. Meanwhile, several therapeutic options by targeting these key factors and molecules were discussed for HCC treatment. Overall, obesity, T2DM, and CVDs as chronic metabolic disease factors are tightly implicated in the development of HCC and its progression. Molecules and factors involved in these NAFLD comorbidities are potential therapeutic targets for HCC treatment.

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Targeting T Cell Subtypes for NAFLD and NAFLD-Related HCC Treatment: An Opinion

Cited by 13 publications

References 73 publications

Inflammatory microenvironment and immunotherapy in hepatocellular carcinoma

Inflammatory microenvironment and immunotherapy in hepatocellular carcinoma

Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma

Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options

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