Two independent reports from NYU Langone researchers revealed that cancer cells activate an integrated stress response (ISR) that triggers ATF4‑dependent secretion of lipocalin 2 (LCN2), which in turn reprograms tumor‑associated macrophages into an immunosuppressive phenotype. Preclinical models showed that blocking LCN2 restored T cell infiltration and improved responses to checkpoint blockade. Authors report LCN2 as a principal ATF4 effector that impairs anti‑tumor immunity in lung and pancreatic cancer models; inhibiting this axis sensitized tumors to immunotherapy in mice. The work suggests targeting stress‑induced secreted factors could complement existing immuno‑oncology strategies and provides a preclinical rationale for developing LCN2‑directed therapies or combining ISR modulators with checkpoint inhibitors.