Analysis of tumor patient samples further validates the negative correlation between ESM1 and CD8+ T cell levels in cancer patients.<h4>Conclusion</h4>In summary, lactate activates the Akt1-Murine Double Minute 2 (MDM2)-p53 pathway via ESM1 to suppress DDR, while the reduction of DDR-generated dsDNA inactivates the cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) pathway, thereby inhibiting CD8+ T cell immune infiltration. Here, MDM2 is linked to cancer.