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12 reviewsSUMMARYThe detailed mechanisms underlying the regulatory significance of dietary components in modulating antitumor immunity remain largely unknown. Here, we apply a co-culture-based screening approach using ablood nutrient compound library and identify zeaxanthin (ZEA), a dietary carotenoid pigment found inmany fruits and vegetables and known for its role in eye health, as an immunomodulator that enhancesthe cytotoxicity of CD8+ T cells against tumor cells. Oral supplementation with ZEA, but not its structural isomer lutein (LUT), enhances anti-tumor immunity in vivo. Integrated multi-omics mechanistic studies revealthat ZEA promotes T cell receptor (TCR) stimulation on the CD8+ T cell surface, leading to improved intracellular TCR signaling for effector T cell function. Hence, ZEA treatment augments the efficacy of anti-PD1 immune checkpoint inhibitor in vivo and the cytotoxicity of human TCR gene-engineered CD8+ T cells in vitro.Our findings uncover a previously unknown immunoregulatory function of ZEA, which has translationalpotential as a dietary element in bolstering immunotherapy.
