Interestingly, in line with our findings, elevated SAM and MTA denote for T cell exhaustion in HCC cancer,44 and MAT2A KO results in obstruction of T cell exhaustion and curbs tumor formation in mice by reducing SAM/MTA in liver.44,45 In addition, HCC induced by glycine N-methyltransferase (GNMT) KO in mice also displays increase of SAM and SAM-polyamine metabolic axis is critical to GNMT-null HCC.46 The discrepancies of the findings are probably due to differences of participated populations in clinical analysis or tumor heterogeneity. Here, MAT2A is linked to hepatocellular carcinoma.