Two linked papers in Nature Biotechnology describe an engineered Escherichia coli Nissle 1917 strain carrying a synthetic arginine‑nitric oxide (NO) circuit that sustains intratumoral NO production. The bacterial platform promoted vascular normalization, reprogrammed immune populations and synergized with anti‑PD‑L1 therapy to reinvigorate CD8+ T cells and drive tumor regressions in mouse models. Authors demonstrated circuit design, intratumoral delivery and immune readouts, positioning programmed microbiota as a modality to modify the tumor microenvironment and potentiate checkpoint immunotherapy in solid tumors.