Conversely, in the context of immunotherapy, TMAO sensitizes tumors to ICB: in triple-negative breast cancer, higher intra-tumoral/plasma TMAO associates with an activated immune microenvironment, and TMAO triggers PERK-dependent ER stress/pyroptosis to strengthen CD8+ cytotoxicity and improve anti-PD-1 efficacy; [178] in PDAC, TMAO upregulates type-I IFN regulators, promotes immunostimulatory TAMs and effector T cells, and synergizes with anti-PD-1/anti-Tim-3 to reduce tumor burden and extend survival [34]. Here, EIF2AK3 is linked to neoplasm.