The effect of oral supplementation of Zeaxanthin on the composition of the mice gut microbiota

The detailed mechanisms underlying regulatory significance of dietary components in modulating anti-tumor immunity remain largely unknown. Here, we applied a co-culture screen approach using a blood nutrient compound library to identify zeaxanthin, a dietary carotenoid pigment found in many fruits and vegetables that is important for eye health, as an immunomodulator that enhances cytotoxicity of CD8+ T cells towards tumor cells. Oral zeaxanthin, but not lutein, a carotenoid with similar structure, enhances anti-tumor immunity in vivo. Integrated multi-omics mechanistic studies reveal that zeaxanthin directly promotes T-cell receptor (TCR) stimulation on CD8+ T cell surface, leading to improved intracellular TCR signaling for effector T cell function. In addition, We found that oral supplementation of ZEA does not affect the composition of the gut microbiota. Hence, zeaxanthin treatment augments effectiveness of immune checkpoint inhibitor in vivo and human TCR-engineered CD8+ T cells to induce cell death in co-cultured tumor cells. Our findings uncover a previously unknown immunoregulatory function of zeaxanthin, which has translational potential as a dietary element in immunotherapy.