ERBB2 and neoplasm: Inhibition of STING with H151 reversed these effects, confirming its critical role in modulating ATPIF1-mediated functions in Her2-targeting CAR-T cells.<h4>Conclusion</h4>Our findings highlight the dual role of ATPIF1 in CAR-T cell therapy: while its overexpression boosts metabolic activity <i>in vitro</i>, its knockdown enhances adaptability to the hypoxic tumor microenvironment <i>in vivo</i>, indicating the paradox for modulating the antitumor activities of CAR-T cells via the metabolic remodeling for the treatment of solid tumor.