Figure 5.

Biological processes that are enriched in patients with long PFS, their interaction, and shared components (e.g., One-carbon metabolism, BCAA biosynthesis, and TCA cycle) between gut microbiota and host cells (e.g., T cells). Methanogenesis generates serine, which enters one-carbon metabolism, and lysine, which enters the aspartate pathway. The aspartate pathway produces methionine which enters the methionine cycle of one-carbon metabolism. In addition, along with BCAA biosynthesis, it generates isoleucine that feeds the TCA cycle. BCAA biosynthesis pathway also produces valine and leucine that enter the TCA cycle. Finally, NADH/NADPH connect one-carbon metabolism, TCA cycle, and BCAA biosynthesis pathway—three important biological processes that are shared by host cells, including immune cells such as CTLs. These pathways can integrate metabolites/metabolic intermediates directly from gut microbiota, such as NADPH, serine, methionine, etc., and prime CTLs to respond better to ICIs in cancer immunotherapy.