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Regulatory T cell: a double-edged sword from metabolic-dysfunction-associated steatohepatitis to hepatocellular

Han Wang1, Allan Tsung2, Lopa Mishra3

  • 1Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Ebiomedicine
|February 24, 2024
PubMed

Insights

Metabolic-dysfunction-associated steatotic liver disease (MASLD) progresses to MASH, increasing liver cancer risk. Regulatory T cells (Tregs) show a dual role in MASH-associated hepatocellular carcinoma (HCC) development, offering potential therapeutic targets.

Area of Science:

  • Hepatology
  • Immunology
  • Oncology

Background:

  • Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, often progressing to metabolic-dysfunction-associated steatohepatitis (MASH).
  • MASH is characterized by inflammation, metabolic dysregulation, and liver regeneration, significantly elevating the risk of hepatocellular carcinoma (HCC).
  • The intricate mechanisms of cancer cell survival within the MASH inflammatory milieu are not fully understood.

Purpose of the Study:

  • To review the dynamic role of regulatory T cells (Tregs) throughout the progression from MASLD to MASH and HCC.
  • To elucidate the paradoxical functions of Tregs in modulating inflammation and immune evasion in the context of MASH-induced liver cancer.
  • To identify potential clinical intervention targets based on Treg behavior in MASLD-associated HCC.

Main Methods:

  • Literature review synthesizing recent findings on Treg function in MASLD and MASH.
  • Analysis of studies investigating Treg interactions within the liver microenvironment during disease progression.
  • Exploration of the dual role of Tregs in inflammation and cancer cell evasion.

Main Results:

  • Regulatory T cells (Tregs) exhibit stage-specific and context-dependent behaviors in MASLD.
  • Tregs demonstrate a paradoxical role, potentially inhibiting tumor-promoting inflammation while also facilitating cancer cell evasion.
  • Distinct Treg activities are observed at different phases of MASLD, influencing the transition to MASH and HCC.

Conclusions:

  • Understanding the multifaceted role of Tregs in MASLD and MASH is crucial for comprehending HCC pathogenesis.
  • Targeting specific Treg functions could offer novel therapeutic strategies for preventing or treating MASH-associated HCC.
  • Further research into Treg dynamics may unlock new avenues for clinical intervention in liver disease progression.
Keywords:
Hepatocellular carcinomaImmunotherapyMetabolic-dysfunction-associated steatohepatitisMetabolic-dysfunction-associated steatotic liver diseaseRegulatory T cell

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