Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Unraveling Molecular Pathways, Immunometabolic Processes, and Their Significance in Immunotherapy for Hepatocellular Carcinoma (HCC)

Abstract

Hepatocellular carcinoma (HCC) is a major global health concern, and understanding the complex interplay of immune cells within the tumor microenvironment is crucial. This review explores the roles of myeloid-derived suppressor cells (MDSCs) and macrophages in HCC, focusing on their molecular pathways, immunometabolic processes, and implications for immunotherapy. We begin by elucidating the origin, expansion, and immunosuppressive mechanisms of MDSCs, emphasizing the importance of molecular pathways and immunometabolism in regulating their functions. In parallel, we delve into the dual nature of tumor-associated macrophages (TAMs) and discuss the molecular and metabolic cues governing their plasticity. Tumor metabolism is a central theme, with a comprehensive overview of altered metabolic processes in cancer cells and their impact on immune cells in the tumor microenvironment. We examine the metabolic crosstalk between tumor cells, MDSCs, and macrophages, shedding light on how tumor metabolism contributes to immune evasion. Furthermore, we discuss the challenges and limitations faced in the clinical application of immunotherapy in HCC. In conclusion, this review highlights the intricate web of molecular pathways and immunometabolic processes shaping the functions of MDSCs and macrophages in HCC. Understanding these dynamics is essential for the innovative immunotherapeutic interventions in HCC, improving outcomes of this devastating disease.