Immunometabolism: A novel perspective of liver cancer microenvironment and its influence on tumor progression

Abstract

The initiation and progression of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are dependent on its tumor microenvironment. Immune cells are key players in the liver cancer microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells are closely related to cell metabolism. However, the effects of metabolic changes of immune cells on liver cancer progression are largely undefined. In this review, we summarize the recent findings of immunometabolism and relate these findings to liver cancer progression. We also explore the translation of the understanding of immunometabolism for clinical use.

Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: A review

“…Recent studies have established that metabolic restrains, such as glucose restriction, impair the activities of effector T cells in TME . In the same context, the remarkable expansion of activated Treg cells, which is characterized by the expression of CD4, CD25, cytotoxic T lymphocyte‐associated protein 4 (CTLA‐4) and forkhead box P3 (FoxP3) in tumour tissues, has been described in both mice and humans, thereby contributing to the suppression of protective anti‐tumour immunity . CD8 + T cells are the most important executors of the anti‐tumour adaptive immunity, including HCC.…”

“…Evidence collected in several types of solid tumours indicated the importance of tumour immunometabolic reprogramming and suggested a novel and crucial area for future research of liver cancer. 48 The complicated crosstalk between meta-…”

“…120 Besides, inhibition of FAO by etomoxir or other methods (such as targeted delivery of CPT1A siRNA/shRNA) may limit the immunosuppressive function of M2 macrophages, which may be developed as an effective therapeutic strategy. 48 Some immunotherapies related to lipid metabolism for cancers were summarized in Table 2. Nonetheless, in consideration of the genotypic and tumour-biological diversities of HCC patients, as well as the complex lipid metabolism, therapeutic strategies targeting the FArelated pathways against HCC still lag behind.…”

“…Treg cells, which is characterized by the expression of CD4, CD25, cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and forkhead box P3 (FoxP3) in tumour tissues, has been described in both mice and humans, thereby contributing to the suppression of protective anti-tumour immunity 48,84. CD8 + T cells are the most important executors of the anti-tumour adaptive immunity, including HCC.…”

“…CD8 + T cells are the most important executors of the anti-tumour adaptive immunity, including HCC. Compared with normal liver, tumour tissue has a lower CD8 + T cells density whereas a higher Tregs density, which indicates dismal prognosis 48. According to previous studies, the exhausted CD8 + T cells infiltrating in HCC are marked by the down-regulated expression of multiple FASs and the decreased intracellular FAs content, as well as functional exhaustion linked with reduced interferon-γ secretion while up-regulated PD-1 expression 85,86.…”