THE ROLE OF IMMUNE CELLS IN OBESITY-RELATED LIVER CANCER

 Introduction: Obesity is an established independent risk factor for hepatocellular carcinoma (HCC), the third leading cause of cancer-related mortality worldwide. In Kazakhstan, where obesity affects over 20% of the adult population and liver cancer incidence has risen steadily, this association carries urgent public health significance. Despite a well-documented epidemiological link, the mechanisms by which obesity undermines antitumor immunity and reshapes the hepatic microenvironment remain incompletely characterized. This review analyses how innate and adaptive immune populations are remodeled across the NAFLD-to-HCC continuum under chronic metabolic stress.

Objective: Analysis of current scientific evidence on the role of immune and inflammatory mechanisms in the development of liver cancer in the context of obesity, and systematization of data on how metabolic disturbances influence antitumor immune responses and the hepatic microenvironment.

Materials and methods:  A systematic literature search was conducted across PubMed, Google Scholar, Scopus, and Web of Science databases, covering international and domestic publications from 2000 to 2026.

Results and discussion: Obesity-associated HCC develops through a progressive immunometabolic cascade in which visceral adipose tissue assembles an immunosuppressive microenvironment – via expansion of myeloid-derived suppressor cells (MDSC), NK cell dysfunction, and CD8⁺ T cell exhaustion – before malignant transformation occurs. Tregs are depleted in obese adipose tissue yet accumulate in HCC; NK cell activation in NASH drives hepatocyte damage rather than tumor protection. Functional polarisation state, not cellular abundance, determines the pathological outcome.

Conclusions: Obesity promotes HCC through chronic adipose inflammation, insulin resistance, and metabolic reprogramming of the tumor microenvironment, exhausting cytotoxic CD8⁺ T cells and NK cells while expanding immunosuppressive Tregs and MDSCs. Liver cancer progression is driven not only by viral or toxic factors but by obesity-induced immune imbalance in which systemic metabolic stress becomes a key enabler of tumor immune evasion.

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