Mus musculus Raw sequence reads
Tumor immunotherapy, especially aPDL1 mediated immune checkpoint blockade, struggles with the immunosuppressive tumor microenvironment, characterized by abnormal vasculature and T cell exhaustion. These issues hinder immune cell infiltration and impair T cell function. Traditional treatments have limited effectiveness and complex requirements, increasing patient burden and outcome uncertainty. To address this, we engineered Escherichia coli Nissle 1917 to self supply arginine and stably produce nitric oxide in tumors, named ECNNO. ECNNO colonization normalized tumor vasculature, enhanced immune cell infiltration, and improved the TME. Combined with aPDL1 therapy, ECNNO boosted antitumor immune responses, reversed T cell exhaustion, and expanded functional memory T cells. This approach extends vascular normalization, optimizes the immunotherapy window, and offers a promising solution to overcome immunotherapy resistance.