Fig. 2: The immunological microenvironment of hepatocellular carcinoma.

In the HCC liver microenvironment, a large population of immune cells, Th17 cells, Tregs, iNKT cells, TAMs, and neutrophils are activated. However, immune cells with antitumor functions such as NK cells, CD8⁺ T cells, and KCs are mostly defective. The number of NK cells is decreased, and their function is suppressed by Tregs and MDSCs. KCs have dual roles in the tumor microenvironment. These cells secrete IL-6 to promote tumor development. KCs also have antitumor functions. However, the antitumor function of KCs is suppressed by MDSCs. CD8⁺ T cells can directly inhibit tumor growth by secreting granular components and cytokines. However, these cells are suppressed by Tregs in the HCC microenvironment. TAMs play various roles during HCC progression, including affecting angiogenesis. Neutrophils can also induce angiogenesis while attracting protumorigenic cells, such as TAMs and Tregs. These immune cells play various roles and can exacerbate HCC development by supporting tumor growth, progression, and angiogenesis.