Natural Killer T Cells in Various Mouse Models of Hepatitis

Guan, Jun; Gang, Wang; Yang, Qin; Chen, Chao; Deng, Jingwen; Gu, Xinyu; Zhu, Haihong

doi:10.1155/2021/1782765

Cited by 8 publications

(8 citation statements)

References 81 publications

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“…NKT cells account for 20% of all intrahepatic lymphocytes and have a unique subset of mature CD4+ T cells that can simultaneously express both NK cell-surface proteins and T cell receptors (TCRs) [ 33 , 34 ]. Hepatocytes express large amounts of CD1d, a member of the major MHC class I-like molecule family, which specifically contains lipid antigens [ 35 ].…”

Section: The Constituent Cells and The Immune Microenvironment In The Livermentioning

confidence: 99%

“…Type I NTK cells recognize self-lipids and microbial lipid antigens, and α-galactosyl ceramide (GalCer) is the most effective ligand for their activation [ 36 ]. Activated type I NKT cells produce various inflammatory cytokines that subsequently stimulate pit cells, lymphocytes, and DCs [ 34 ]. In contrast, type II NKT cells express various TCRs that activate self-lipids, cannot express α-GalCer [ 35 , 36 ] and are more likely to produce Th1 cytokines, which inhibit the activation of proinflammatory type I NKT cells and protect against liver injury [ 34 , 36 ].…”

Section: The Constituent Cells and The Immune Microenvironment In The Livermentioning

confidence: 99%

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Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review

Oura

Morishita

Tani

et al. 2021

IJMS

266

180

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Liver cancer has the fourth highest mortality rate of all cancers worldwide, with hepatocellular carcinoma (HCC) being the most prevalent subtype. Despite great advances in systemic therapy, such as molecular-targeted agents, HCC has one of the worst prognoses due to drug resistance and frequent recurrence and metastasis. Recently, new therapeutic strategies such as cancer immunosuppressive therapy have prolonged patients’ lives, and the combination of an immune checkpoint inhibitor (ICI) and VEGF inhibitor is now positioned as the first-line therapy for advanced HCC. Since the efficacy of ICIs depends on the tumor immune microenvironment, it is necessary to elucidate the immune environment of HCC to select appropriate ICIs. In this review, we summarize the findings on the immune microenvironment and immunosuppressive approaches focused on monoclonal antibodies against cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1 for HCC. We also describe ongoing treatment modalities, including adoptive cell transfer-based therapies and future areas of exploration based on recent literature. The results of pre-clinical studies using immunological classification and animal models will contribute to the development of biomarkers that predict the efficacy of immunosuppressive therapy and aid in the selection of appropriate strategies for HCC treatment.

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Section: The Constituent Cells and The Immune Microenvironment In The Livermentioning

confidence: 99%

Section: The Constituent Cells and The Immune Microenvironment In The Livermentioning

confidence: 99%

Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review

Oura

Morishita

Tani

et al. 2021

IJMS

266

180

View full text Add to dashboard Cite

show abstract

“…The iNKT cells release cytokines that can alter the polarization and activation of immune cells, especially NK and T cells. Indeed, they are a unique sub-population of mature CD4 + T cells that can simultaneously express both NK cell surface markers and TCRs [76,77].…”

Section: Invariant Natural Killer T Cellsmentioning

confidence: 99%

“…Type I NKT cells recognize self-lipids and microbial lipid antigens. Activated type I NKT cells release proinflammatory cytokines that stimulate pit cells, lymphocytes, and DCs [77]. On the other hand, type II NKT cells can release cytokines that suppress immune responses [77,78].…”

Section: Invariant Natural Killer T Cellsmentioning

confidence: 99%

Immunotherapy for Hepatocellular Carcinoma: New Prospects for the Cancer Therapy

Fasano

Baradaran

Brunetti

et al. 2021

Life

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. HCC patients may benefit from liver transplantation, hepatic resection, radiofrequency ablation, transcatheter arterial chemoembolization, and targeted therapies. The increased infiltration of immunosuppressive immune cells and the elevated expression of immunosuppressive factors in the HCC microenvironment are the main culprits of the immunosuppressive nature of the HCC milieu. The immunosuppressive tumor microenvironment can substantially attenuate antitumoral immune responses and facilitate the immune evasion of tumoral cells. Immunotherapy is an innovative treatment method that has been promising in treating HCC. Immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), and cell-based (primarily dendritic cells) and non-cell-based vaccines are the most common immunotherapeutic approaches for HCC treatment. However, these therapeutic approaches have not generally induced robust antitumoral responses in clinical settings. To answer to this, growing evidence has characterized immune cell populations and delineated intercellular cross-talk using single-cell RNA sequencing (scRNA-seq) technologies. This review aims to discuss the various types of tumor-infiltrating immune cells and highlight their roles in HCC development. Besides, we discuss the recent advances in immunotherapeutic approaches for treating HCC, e.g., ICIs, dendritic cell (DC)-based vaccines, non-cell-based vaccines, oncolytic viruses (OVs), and ACT. Finally, we discuss the potentiality of scRNA-seq to improve the response rate of HCC patients to immunotherapeutic approaches.

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“…NKT cells are a unique innate-like lymphoid cell population sharing both NK cell and T cell attributes. NKT cells take part in the regulation of liver immunity during viral hepatitis by direct cytotoxicity and the production of large quantities of cytokines, including mediators for enhanced neutrophil infiltration [ 119 , 120 ]. In acute HEV infection, patients show decreased counts of circulating NKT cells, whereas activation is markedly increased [ 121 ].…”

Section: Immune Responses Induced Against Hevmentioning

confidence: 99%

Hepatitis E Virus Infection—Immune Responses to an Underestimated Global Threat

Kupke

Werner

2021

Cells

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Infection with the hepatitis E virus (HEV) is one of the main ubiquitous causes for developing an acute hepatitis. Moreover, chronification plays a predominant role in immunocompromised patients such as transplant recipients with more frequent severe courses. Unfortunately, besides reduction of immunosuppression and off-label use of ribavirin or pegylated interferon alfa, there is currently no specific anti-viral treatment to prevent disease progression. So far, research on involved immune mechanisms induced by HEV is limited. It is very difficult to collect clinical samples especially from the early phase of infection since this is often asymptomatic. Nevertheless, it is certain that the outcome of HEV-infected patients correlates with the strength of the proceeding immune response. Several lymphoid cells have been identified in contributing either to disease progression or achieving sustained virologic response. In particular, a sufficient immune control by both CD4+ and CD8+ T cells is necessary to prevent chronic viral replication. Especially the mechanisms underlying fulminant courses are poorly understood. However, liver biopsies indicate the involvement of cytotoxic T cells in liver damage. In this review, we aimed to highlight different parts of the lymphoid immune response against HEV and point out questions that remain unanswered regarding this underestimated global threat.

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Natural Killer T Cells in Various Mouse Models of Hepatitis

Cited by 8 publications

References 81 publications

Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review

Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review

Immunotherapy for Hepatocellular Carcinoma: New Prospects for the Cancer Therapy

Hepatitis E Virus Infection—Immune Responses to an Underestimated Global Threat

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