Fig. 1

Brief overview of the immune evasion mechanisms in hepatocellular carcinoma (HCC). Various ways through which HCC manipulates the tumor immune microenvironment (TIME) and eludes immune monitoring are demonstrated. Important immune-suppressive molecules that lead to the suppression of T cell activation and induction of T cell exhaustion are increased on tumor cells and infiltrating immune cells. These molecules include PD-L1/PD-1, CTLA-4/B7, and TIM-3/Galectin-9. TIME is additionally distinguished by a significant influx of immune-suppressive cells, including as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and tumor-associated macrophages (TAMs), which secrete cytokines such as VEGF, IL-10, and TGF-β. These cytokines promote angiogenesis, tumor development, and immune suppression. Furthermore, extracellular matrix elements and angiogenic factors like VEGF are secreted by cancer-associated fibroblasts (CAFs) and TAMs in the TIME, which helps to physically exclude immune cells from the tumor core and strengthens the immunosuppressive environment. CAFs also release additional immunosuppressive cytokines and chemokines, such as IL-6 and CXCL12, which further suppress T cell infiltration and enhance the recruitment of other immunosuppressive cells like Tregs and TAMs. By reducing glucose, HCC cells also provide an environment that is metabolically unfavorable, which inhibits effector T cell function and fosters an immunosuppressive phenotype