Myeloid cell MHC I expression drives CD8+ T cell activation in nonalcoholic steatohepatitis

Adams, Victoria R.; Collins, Leonard B.; Williams, Taufika Islam; Holmes, Jennifer; Hess, Paul; Atkins, Hannah M.; Scheidemantle, Grace; Liu, Xiaojing; Lodge, Mareca; Johnson, Aaron J.; Kennedy, Arion

doi:10.3389/fimmu.2023.1302006

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…Kupffer cells and other tumor associated macrophages (TAMs) are involved in hepatocarcinogenesis and immune evasion in different mechanisms including secreting immunosuppressive mediators, expressing programmed death-ligand 1 (PD-L1), recruiting Tregs as well as IL-17-expressing CD4+ T helper 17 (Th17), and downregulating MHC II expression along with costimulatory molecules ( 20 ). In non-alcoholic steatohepatitis (NASH), a subset of activated CD8+ T expressing exhaustion marker PD-1 are elevated ( 28 ). These cells exert an auto-aggressive behavior and drive necro-inflammation by secreting tumor necrosis factor alpha (TNF-α).…”

Section: Tumor Microenvironment In Hepatocellular Carcinomamentioning

confidence: 99%

Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

Akbulut,

Aru,

Aydın

et al. 2024

Front. Immunol.

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Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.

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Section: Tumor Microenvironment In Hepatocellular Carcinomamentioning

confidence: 99%

Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

Akbulut,

Aru,

Aydın

et al. 2024

Front. Immunol.

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Ag-driven CD8+ T cell clonal expansion is a prominent feature of MASH in humans and mice

Burtis,

DeNicola,

Ferguson

et al. 2024

Hepatology

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Background and Aims: Chronic liver disease due to metabolic dysfunction–associated steatohepatitis (MASH) is a rapidly increasing global epidemic. MASH progression is a consequence of the complex interplay between inflammatory insults and dysregulated hepatic immune responses. T lymphocytes have been shown to accumulate in the liver during MASH, but the cause and consequence of T cell accumulation in the liver remain unclear. Our study aimed to define the phenotype and T cell receptor diversity of T cells from human cirrhotic livers and an animal model of MASH to begin resolving their function in disease. Approach and Results: In these studies, we evaluated differences in T cell phenotype in the context of liver disease. Accordingly, we isolated liver resident T cell populations from humans with cirrhosis and from mice with diet-induced MASH. Using both 5’ single-cell sequencing and flow cytometry, we defined the phenotype and T cell receptor repertoire of liver resident T cells during health and disease. Conclusions: MASH-induced human cirrhosis and diet-induced MASH in mice resulted in the accumulation of activated and clonally expanded T cells in the liver. The clonally expanded T cells in the liver expressed markers of chronic antigenic stimulation, including PD1, TIGIT, and TOX. Overall, this study establishes for the first time that T cells undergo Ag-dependent clonal expansion and functional differentiation during the progression of MASH. These studies could lead to the identification of antigenic targets that drive T cell activation, clonal expansion, and recruitment to the liver during MASH.

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Myeloid cell MHC I expression drives CD8+ T cell activation in nonalcoholic steatohepatitis

Cited by 2 publications

References 52 publications

Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

Ag-driven CD8+ T cell clonal expansion is a prominent feature of MASH in humans and mice

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