Core Viewpoint - The article discusses a study published in Nature Biotechnology that highlights the development of engineered E. coli (ECN-NO) capable of sustained nitric oxide production, which remodels the tumor microenvironment and enhances the effectiveness of cancer immunotherapy [2][4]. Group 1 - The research team engineered the E. coli Nissle 1917 strain to create ECN-NO, which continuously produces nitric oxide by modifying the arginine synthesis pathway [4]. - The mechanism involves knocking out the arginine repressor protein ArgR to relieve feedback inhibition on arginine biosynthesis, while co-expressing arginine succinate synthase/lyase (ArgG/ArgH) and Bacillus subtilis nitric oxide synthase (BsNOS) to enhance arginine regeneration [4]. - ECN-NO significantly improves the anti-tumor effects of anti-PD-L1 (αPD-L1) immunotherapy in various solid tumor mouse models, achieving durable tumor regression [4]. Group 2 - Mechanistic studies indicate that ECN-NO induces vascular normalization and recruits dendritic cells (DCs), alleviating tumor immune suppression [4]. - It synergistically amplifies functional CD8+ T cells, reverses T cell exhaustion, and promotes the formation of memory T cells, establishing sustained anti-tumor immune memory for at least 120 days [4].