Figure 1.

In the tumor microenvironment of hepatocellular carcinoma, various cells indirectly promote the escape of tumor cells by regulating T cells. This includes tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and Kupffer cells, which release cytokines such as TGF-β and IL-10, as well as chemokines like CCL22. Additionally, Tregs directly promote tumor cell escape by secreting immunosuppressive cytokines, including TGF-β, IL-10, and IL-35. On one hand, tregs secrete TGF-β and IL-10 to stimulate cancer-associated fibroblasts (CAFs). These CAFs then produce collagen and extracellular matrix components, which facilitate tumor cell escape. On the other hand, tregs inhibit the cytotoxic activity of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs), and CD8⁺T cells against tumor cells through the secretion of TGF-β and proteins such as FGL2.