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Background The industrialized diet often contains imbalanced levels of certain micronutrients, which can significantly influence the composition of the gut microbiota and immune responses. These interactions have profound implications for cancer immunity, which is the focus of this study. Specifically, this study investigates the effects of sodium (Na) and zinc (Zn) on tumor immunity, with a focus on how they interact with the gut microbiome.Methods To investigate the effects of sodium and zinc on tumor immunity, we first measured the levels of these micronutrients in industrialized diets using ICP-MS. Experimental animals were fed a customized research diet containing equivalent amounts of sodium and zinc. Stool samples were collected for metagenomics and metabolomics analysis using NGS and LC-MS/GC-MS, respectively. Pseudogerm-free mice, fecal microbiota transplantation (FMT), and monoclonal antibody-mediated neutralization were used for further evaluation. In vitro differentiation of CD4+ T cells, CD8+ T cells, NK cells, and other immune cells was conducted, followed by deep analysis using high-end flow cytometry and RT-PCR to study the direct effects of these micronutrients on immune cells.Results The study found that high sodium intake enhances NK cell-mediated tumor immunity by inhibiting PD-1 expression and increasing IFN-γ production. The antitumor response strongly correlated with serum hippurate levels. Depleting the gut microbiota weakened these effects, but they were restored through FMT from mice on a sodium-rich diet. High sodium intake also increased the abundance of Bifidobacterium, which localized within the tumor microenvironment due to increased gut permeability. This localization facilitated NK cell infiltration and enhanced their antitumor function. Furthermore, both high and deficient zinc levels were shown to influence Foxp3+ Tregs. Zinc chelation with chloroquine (CQ) also enhanced the response to α-PD-1 immunotherapy, particularly in melanoma models.Conclusions High sodium intake enhances NK cell-mediated antitumor immunity by suppressing PD-1, increasing IFN-γ, and promoting tumor infiltration of Bifidobacterium via gut permeability. These effects depend on the microbiota and correlate with serum hippurate levels. Zinc levels also modulate Treg function, and zinc chelation with chloroquine boosts α-PD-1 immunotherapy, highlighting dietary and microbial modulation as potential strategies to enhance cancer immunotherapy.