Researchers at NYU Langone identified lipocalin 2 (LCN2) as a major effector of the integrated stress response (ISR) that enables lung and pancreatic tumors to evade immune attack. Published in Nature, the preclinical work shows ATF4-driven expression of LCN2 reprograms tumor‑associated macrophages toward an immunosuppressive phenotype and excludes cytotoxic T cells. Genetic and pharmacologic blockade of LCN2 in mouse models slowed tumor growth and synergized with checkpoint immunotherapies, restoring T cell infiltration. Investigators propose LCN2 as a druggable node linking cancer cell stress pathways to immune suppression, with translational potential for combination strategies. For immuno-oncology developers, targeting ISR effectors such as LCN2 offers a new angle to overcome myeloid-driven resistance; the findings could spur antibody, small‑molecule or biologic approaches aimed at reshaping the tumor microenvironment to improve checkpoint efficacy.