Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses

Int J Mol Sci. 2023 Apr 18;24(8):7463. doi: 10.3390/ijms24087463.

Abstract

Hepatocellular carcinoma is the most common primary liver cancer, ranking third among the leading causes of cancer-related mortality worldwide and whose incidence varies according to geographical area and ethnicity. Metabolic rewiring was recently introduced as an emerging hallmark able to affect tumor progression by modulating cancer cell behavior and immune responses. This review focuses on the recent studies examining HCC's metabolic traits, with particular reference to the alterations of glucose, fatty acid and amino acid metabolism, the three major metabolic changes that have gained attention in the field of HCC. After delivering a panoramic picture of the peculiar immune landscape of HCC, this review will also discuss how the metabolic reprogramming of liver cancer cells can affect, directly or indirectly, the microenvironment and the function of the different immune cell populations, eventually favoring the tumor escape from immunosurveillance.

Keywords: HCC; TCA cycle; amino acid metabolism; fatty acid metabolism; glucose metabolism; glutamine; immune response; metabolic reprogramming; tumor microenvironment; urea cycle.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular* / metabolism
  • Glycolysis
  • Humans
  • Immunity
  • Liver Neoplasms* / metabolism
  • Tumor Microenvironment