ECN Coated with Met Can Inhibit PD-L1 Expression in Tumor Cells and Enhance Immune-Mediated Antitumor Effects in CT26...

Currently, the live treatment strategy based on Escherichia coli Nissle 1917 (ECN) is widely researched in the field of tumor therapy based on its outstanding tumor targeting and colonization ability. ECN can serve as an immunological adjuvant, releasing self-antigens and related metabolic products to stimulate immune responses at tumor sites to break the immunosuppressive microenvironment. However, the propensity for ECN to colonize tumor sites might inadvertently stimulate IFN-γ production, leading to an upregulation of PD-L1 expression in tumor cells, which could suppress immune cell activity and foster immune evasion. To solve this problem, we encapsulate ECN with a hybrid film of metformin (Met) and a Lipo membrane by electrostatic adsorption to inhibit expression of PD-L1 in the tumor. In vivo experiments show that ECN can specifically colonize the core of the tumor and effectively deliver Met to the core of the tumor, enhancing the Met penetration ability in the tumor. On the other hand, Met inhibits the expression of PD-L1 in tumor cells, reverses the immune suppressive microenvironment of the tumor, and recruits CD3⁺ CD4⁺ CD8⁺ T lymphocyte cells to infiltrate the tumor site, ultimately enhancing the antitumor response.