Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma

Mirshahi, Faridoddin; Aqbi, Hussein F.; Isbell, Madison; Manjili, Saeed H.; Guo, Chunqing; Saneshaw, Mulugeta; Dozmorov, Mikhail G.; Khosla, Archit; Wack, Katy; Carrasco-Zevallos, Oscar; Idowu, Michael O.; Wang, Xiangyang; Sanyal, Arun J.; Manjili, Masoud H.; Bandyopadhyay, Dipankar

doi:10.1016/j.celrep.2022.110454

Cited by 24 publications

(32 citation statements)

References 53 publications

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“…Chronic injury and the associated inflammatory responses are a major link between liver steatosis and cancer development. The development of liver cancer is a slow process that evolves from premalignant lesions developed within chronically damaged livers ( 83 ). In chemical induced hepatocarcinogenesis, HFD feeding promotes hepatic inflammation and exacerbates tumor development ( 84 ).…”

Section: Macrophage Response To Steatotic Liver Injury: a Double-edge...mentioning

confidence: 99%

“…They also secrete proinflammatory cytokines including TNFα, IL-6, IL-8 as well as IL-1 consistent with a role in the wound healing response where proinflammatory cytokines induce hepatocyte proliferation for tissue repair. In mice fed a Western diet, tumor progression is associated with a predominant M1 proinflammatory cytokine vs. the M2 pattern ( 83 ). In ALD, severe liver damage is also accompanied by significantly elevated M1 proinflammatory macrophage marker expression in C57Bl/6 mice, whereas less damage is observed in Balb/c mice where no change of M1 markers is found ( 104 ).…”

Section: Cytokines In Steatosis Driven Hccmentioning

confidence: 99%

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Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

Alba

Datta

et al. 2022

Front. Oncol.

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Obesity confers an independent risk for carcinogenesis. Classically viewed as a genetic disease, owing to the discovery of tumor suppressors and oncogenes, genetic events alone are not sufficient to explain the progression and development of cancers. Tumor development is often associated with metabolic and immunological changes. In particular, obesity is found to significantly increase the mortality rate of liver cancer. As its role is not defined, a fundamental question is whether and how metabolic changes drive the development of cancer. In this review, we will dissect the current literature demonstrating that liver lipid dysfunction is a critical component driving the progression of cancer. We will discuss the involvement of inflammation in lipid dysfunction driven liver cancer development with a focus on the involvement of liver macrophages. We will first discuss the association of steatosis with liver cancer. This will be followed with a literature summary demonstrating the importance of inflammation and particularly macrophages in the progression of liver steatosis and highlighting the evidence that macrophages and macrophage produced inflammatory mediators are critical for liver cancer development. We will then discuss the specific inflammatory mediators and their roles in steatosis driven liver cancer development. Finally, we will summarize the molecular pattern (PAMP and DAMP) as well as lipid particle signals that are involved in the activation, infiltration and reprogramming of liver macrophages. We will also discuss some of the therapies that may interfere with lipid metabolism and also affect liver cancer development.

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Section: Macrophage Response To Steatotic Liver Injury: a Double-edge...mentioning

confidence: 99%

Section: Cytokines In Steatosis Driven Hccmentioning

confidence: 99%

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

Alba

Datta

et al. 2022

Front. Oncol.

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“…Some studies showed that NAFLD induces CD4 + T cell depletion leading to HCC, such that prevention of CD4 + T cell depletion has been suggested to suppress hepatocarcinogenesis [ 3 , 4 ]. Using a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND), we have also detected a reduced proportion of CD4 + to CD8 + T cells, chronic inflammation, as well as predominant inflammatory T helper 1 cells (Th1), M1 macrophages, and NKT cells during the progression of NAFLD to HCC [ 5 , 6 ]. Interestingly, inhibition of HCC was associated with the modulation of the hepatic immunological pattern towards an equilibrium CD8 + /CD4 + T cells, Th1/Th2/Th17, M1/M2, and NKT/NK cells [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Using a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND), we have also detected a reduced proportion of CD4 + to CD8 + T cells, chronic inflammation, as well as predominant inflammatory T helper 1 cells (Th1), M1 macrophages, and NKT cells during the progression of NAFLD to HCC [ 5 , 6 ]. Interestingly, inhibition of HCC was associated with the modulation of the hepatic immunological pattern towards an equilibrium CD8 + /CD4 + T cells, Th1/Th2/Th17, M1/M2, and NKT/NK cells [ 5 ]. These reports suggest that prevention of CD4 + T cell depletion, modulation of the hepatic immunological pattern, and inhibition of chronic inflammation could prevent the progression of NAFLD to HCC [ 5 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, inhibition of HCC was associated with the modulation of the hepatic immunological pattern towards an equilibrium CD8 + /CD4 + T cells, Th1/Th2/Th17, M1/M2, and NKT/NK cells [ 5 ]. These reports suggest that prevention of CD4 + T cell depletion, modulation of the hepatic immunological pattern, and inhibition of chronic inflammation could prevent the progression of NAFLD to HCC [ 5 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Restoration of CD4+ T Cells during NAFLD without Modulation of the Hepatic Immunological Pattern Is Not Sufficient to Prevent HCC

Isbell

Mirshahi

Aqbi

et al. 2022

Cancers

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Predominant inflammatory immunological patterns as well as the depletion of CD4+ T cells during nonalcoholic fatty liver disease (NAFLD) are reported to be associated with the progression of hepatocellular carcinoma (HCC). Here, we report that an LRP-1 agonistic peptide, SP16, when administered during advanced NAFLD progression, restored the depleted CD4+ T cell population but did not significantly affect the inflammatory immunological pattern. This data suggests that restoration of CD4+ T cells without modulation of the hepatic immunological pattern is not sufficient to prevent HCC. However, SP16 administered early during NAFLD progression modulated the inflammatory profile. Future studies will determine if regulation of the inflammatory immune response by SP16 early in NAFLD progression will prevent HCC.

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Decoding the role of immune T cells: A new territory for improvement of metabolic‐associated fatty liver disease

Liu

Ding

Bai

et al. 2023

iMeta

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Metabolic-associated fatty liver disease (MAFLD) is a new emerging concept and is associated with metabolic dysfunction, generally replacing the name of nonalcoholic fatty liver disease (NAFLD) due to heterogeneous liver condition and inaccuracies in definition. The prevalence of MAFLD is rising by year due to dietary changes, metabolic disorders, and no approved therapy, affecting a quarter of the global population and representing a major economic problem that burdens healthcare systems. Currently, in addition to the common causative factors like insulin resistance, oxidative stress, and lipotoxicity, the role of immune cells, especially T cells, played in MAFLD is increasingly being emphasized by global scholars. Based on the diverse classification and pathophysiological effects of immune T cells, we comprehensively analyzed their bidirectional regulatory effects on the hepatic inflammatory microenvironment and MAFLD progression. This interaction between MAFLD and T cells was also associated with hepatic-intestinal immune crosstalk and gut microbiota homeostasis. Moreover, we pointed out several T-cell-based therapeutic approaches including but not limited to adoptive transfer of T cells, fecal microbiota transplantation, and drug therapy, especially for natural products and Chinese herbal prescriptions. Overall, this study contributes to a better understanding of the important role of T cells played in MAFLD progression and corresponding therapeutic options and provides a potential reference for further drug development.

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Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma

Cited by 24 publications

References 53 publications

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

Restoration of CD4+ T Cells during NAFLD without Modulation of the Hepatic Immunological Pattern Is Not Sufficient to Prevent HCC

Decoding the role of immune T cells: A new territory for improvement of metabolic‐associated fatty liver disease

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