The combination of TGF-B inhibitors significantly enhances the sensitivity of HCC cells to regorafenib and sorafenib (65, 66); (c) CD25 expressed by Tregs competitively consumes IL-2, reduces effector T cell activation, and induces metabolic disorders (67); (d) CD73, CD39, and cyclic AMP-regulated adenosine A2 receptor (A2AR) can reduce T-cell toxicity and shift the microenvironment into a tolerant state (68); (e) Tregs secrete granzyme B/perforin that directly lyses NK and CD8+ T cells (69). The gene discussed is TGFB1; the disease is hepatocellular carcinoma.