<i>In vivo</i>, <i>Atad2</i> deficiency reduced intratumoral LA, remodeled the immunosuppressive microenvironment, increased CD8<sup>+</sup> T cell infiltration, inhibited tumor growth, and improved sensitivity to anti-PD-1 therapy.<h4>Conclusions</h4>ATAD2 drives immunotherapy resistance in LUAD by activating an ATAD2-LDHA-LA axis that impairs CD8<sup>+</sup> T cell function. The gene discussed is LDHA; the disease is neoplasm.