Two companion papers in Nature Biotechnology report an engineered Escherichia coli Nissle strain that produces sustained intratumoral nitric oxide (NO), reshaping the tumor microenvironment to improve immunotherapy efficacy. The synthetic arginine–NO circuit promoted vascular normalization, CD8+ T‑cell reinvigoration, and durable tumor regression in mouse models when combined with PD‑L1 blockade. Authors demonstrated mechanistic links between continuous NO delivery, reduced immunosuppression, and improved drug penetration; experiments included multiple solid‑tumor models. The teams propose microbial biotherapeutics as a means to locally modulate immune metabolism and rescue checkpoint resistance without systemic NO toxicity.