Research and advances in TK1-mediated metabolic reprogramming in modulating the tumor immune microenvironment in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is still one of the leading causes of cancer-related deaths in the world. It is characterized by significant metabolic disorders and immunosuppressive tumor microenvironment(TME). As a key enzyme in the thymidine remedy pathway, TK1 is traditionally regarded as a biomarker related to proliferation. However, recent evidence shows that the biological function of TK1 has gone beyond the category of nucleotide metabolism and may be involved in a variety of processes related to tumor progression. In this review, we summarize the current understanding of the biological function of TK1 and discuss its evolving role in HCC. Let's first examine the classical and non-classical functions of TK1, including its participation in nucleotide homeosism, metabolic adaptation and tumor-related signal networks. Then, we reviewed the recent evidence that TK1 promotes metabolic reprogramming by regulating glycolysis, nucleotide metabolism and a wider range of metabolic signaling pathways. In addition, we discussed how TK1-related metabolic changes can affect the tumor immune microenvironment(TIME) by promoting nutritional competition, lactic acid accumulation, and establishing an immunosuppressive microenvironment involving CD8 + T cells, tumor-related macrophages, regulatory T cells, medullary inhibitory cells and dendritic cells. Importantly, more and more data support the view that TK1 acts as a key node in connecting metabolic reprogramming and immune remodeling in HCC. Collectively, this review proposes a conceptual framework in which TK1 is viewed not merely as a proliferation marker but as a potential regulator of the metabolic–immune ecosystem in HCC. A deeper understanding of TK1-mediated metabolic and immunological interactions may facilitate the development of novel biomarkers and precision therapeutic strategies for patients with HCC.