Metabolic rearrangements and intratumoral heterogeneity for immune response in hepatocellular carcinoma

Liver cancer is one of the most common malignant tumors globally. Not only is it difficult to diagnose, but treatments are scarce and the prognosis is generally poor. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Aggressive cancer cells, such as those found in HCC, undergo extensive metabolic rewiring as tumorigenesis, the unique feature, ultimately causes adaptation to the neoplastic microenvironment. Intratumoral heterogeneity (ITH) is defined as the presence of distinct genetic features and different phenotypes in the same tumoral region. ITH, a property unique to malignant cancers, results in differences in many different features of tumors, including, but not limited to, tumor growth and resistance to chemotherapy, which in turn is partly responsible for metabolic reprogramming. Moreover, the different metabolic phenotypes might also activate the immune response to varying degrees and help tumor cells escape detection by the immune system. In this review, we summarize the reprogramming of glucose metabolism and tumoral heterogeneity and their associations that occur in HCC, to obtain a better understanding of the mechanisms of HCC oncogenesis.

Automated summary

Liver cancer, particularly hepatocellular carcinoma (HCC), is a common and difficult to diagnose malignant tumor with limited treatment options and poor prognosis. Aggressive cancer cells in HCC undergo extensive metabolic rewiring, leading to adaptation to the tumor microenvironment. Intratumoral heterogeneity (ITH), characterized by distinct genetic and phenotypic features in the same tumor region, is unique to malignant tumors and contributes to differences in tumor growth, chemotherapy resistance, and metabolic reprogramming. Understanding the associations between glucose metabolism reprogramming, tumoral heterogeneity, and HCC oncogenesis is crucial for better insights into HCC mechanisms.