Collectively, dietary regulation enhances immunotherapy by targeting two core metabolite-mediated processes: (1) increasing microbial production of immunostimulatory metabolites (SCFAs, ILA/IPA) that activate CD8+ T cells, DCs, and NK cells via HDAC inhibition or AhR/STING signaling; (2) reducing immunosuppressive metabolites (TCA, Kyn) by restricting substrates for pro-tumor microbiota. The gene discussed is HDAC9; the disease is neoplasm.