MTHFD2 and cancer: In addition to SARDH, methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), another enzyme involved in folate metabolism and previously linked to SAM production [65, 66], was also enriched in exhausted CD8+ T cells across all the cancer types we studied (Supplementary Fig. S1G), further indicating the potential link between altered 1-C metabolism and T-cell exhaustion.