Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy

Zhang, Chunye; Liu, Shuai; Yang, Ming

doi:10.3748/wjg.v28.i27.3346

Cited by 20 publications

(15 citation statements)

References 89 publications

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“…HCC is a typical inflammation-associated malignancy with a complex immune microenvironment ( 21 ). Chronic HBV infection and chronic hepatitis C virus infection create a tolerogenic immune microenvironment through T-cell exhaustion (loss of antiviral effector function of virus-specific CD8 + T cells) and viral escape mutations ( 21 , 22 ). ICIs, including PD-1, PD-L1 and CTLA-4, have demonstrated significant therapeutic efficacy in the field of HCC treatment ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor‑associated diabetes mellitus in patients with HCC: Report of three cases and literature review

Wang,

Dong

et al. 2024

Exp Ther Med

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Treatment with immune checkpoint inhibitors (ICIs) is steadily becoming the standard of care for hepatocellular carcinoma (HCC), with an increasing number of immune-related adverse events (irAEs). However, only a small number of reports on the occurrence of diabetes mellitus (DM) in patients with HCC treated with ICIs have been published. In the present study, the clinical manifestations, laboratory findings, treatment and prognosis of three patients with advanced HCC were reported, who suffered immune-related DM when receiving treatment with ICIs. Furthermore, the relevant literature was reviewed in order to summarize clinical manifestations, possible mechanisms, diagnosis, prognosis of rechallenge and recommended management options, as well as clinical treatment suggestions. ICI-induced diabetes is rare but irAEs are potentially fatal, as diabetic ketoacidosis (DKA) is often the first manifestation. The incidence of immune-related DM is 0.86% and among those cases, the incidence of DKA is 59%. The combination of two ICIs markedly increases the risk. The human leukocyte antigen genotype, islet autoantibodies and autoreactive T cell-mediated β-cell destruction may be linked to the occurrence of immune-related DM. Patient education and clinicians' awareness of ICI-related DM are good management options. Adequate clinical judgment, close monitoring and early detection are also needed to decide whether to continue immunotherapy or to rechallenge it, so as to achieve the maximum benefit of clinical treatment.

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Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor‑associated diabetes mellitus in patients with HCC: Report of three cases and literature review

Wang,

Dong

et al. 2024

Exp Ther Med

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“…A large body of literature indicates a correlation between Treg accumulation in tumor tissues and poor prognosis, but some reports associate Tregs with better prognosis in diseases such as hepatocellular carcinoma and colon cancer ( 57 ). The functional heterogeneity of tumor-infiltrating Tregs, the site of infiltration, and detection methods, as well as factors such as levels of CD8+ cytotoxic T cells, tumor cell immunogenicity, and inflammatory infiltration of the tumor microenvironment, can explain these seemingly contradictory results.…”

Section: Regulation Of Tumor Development By Treg Infiltration Into Ca...mentioning

confidence: 99%

Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review

Wu,

Zhou,

Cao

et al. 2023

Front. Immunol.

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Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulation of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body’s anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy.

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“…When Tregs were depleted, HCC initiation and progression of NASH was drastically inhibited ( Wang et al, 2021 ). Furthermore, an imbalance between helper T cells and Tregs can promote progression of NAFLD along with higher expression of inflammatory cytokines ( He et al, 2017 ; Zhang CY. et al, 2022 ).…”

Section: Influence Of Liver Disease On the Hepatic Immune Microenviro...mentioning

confidence: 99%

“…Furthermore, preclinical studies suggest chronic alcohol consumption reduces Tregs and causes an increase in helper T cells ( Chen et al, 2016 ). The molecular mechanisms and full impact of changes in immune subsets on the progression of alcoholic liver disease has not yet been fully elucidated ( Zhang CY. et al, 2022 ).…”

Section: Influence Of Liver Disease On the Hepatic Immune Microenviro...mentioning

confidence: 99%

The effect of liver disease on hepatic microenvironment and implications for immune therapy

Brown,

Ruff,

Pawlik

2023

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth leading cause of cancer-related death worldwide. HCC often occurs in the setting of chronic liver disease or cirrhosis. Recent evidence has highlighted the importance of the immune microenvironment in the development and progression of HCC, as well as its role in the potential response to therapy. Liver disease such as viral hepatitis, alcohol induced liver disease, and non-alcoholic fatty liver disease is a major risk factor for the development of HCC and has been demonstrated to alter the immune microenvironment. Alterations in the immune microenvironment may markedly influence the response to different therapeutic strategies. As such, research has focused on understanding the complex relationship among tumor cells, immune cells, and the surrounding liver parenchyma to treat HCC more effectively. We herein review the immune microenvironment, as well as the relative effect of liver disease on the immune microenvironment. In addition, we review how changes in the immune microenvironment can lead to therapeutic resistance, as well as highlight future strategies aimed at developing the next-generation of therapies for HCC.

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Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy

Cited by 20 publications

References 89 publications

Immune checkpoint inhibitor‑associated diabetes mellitus in patients with HCC: Report of three cases and literature review

Immune checkpoint inhibitor‑associated diabetes mellitus in patients with HCC: Report of three cases and literature review

Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review

The effect of liver disease on hepatic microenvironment and implications for immune therapy

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