Two independent reports published in Nature Biotechnology and Nature detail engineered Escherichia coli Nissle 1917 strains programmed with synthetic arginine–nitric oxide (NO) circuits that deliver sustained intratumoral NO, remodel the tumor microenvironment and sensitize tumors to PD‑L1 checkpoint blockade in mouse models. Authors show bacterially produced NO promotes vascular normalization, reduces immunosuppression, reinvigorates CD8+ T cells and produces durable tumor regressions when combined with anti‑PD‑L1 therapy. The approaches use bacterial colonization of tumors to produce a localized immune‑modulating effector rather than systemic delivery, aiming to limit off‑target toxicity. Researchers note translational hurdles including containment, translatability of microbe‑based delivery in humans, regulatory pathways for engineered live biotherapeutics and rigorous safety assessments required before clinical trials.