Polarization of Tumor-Associated Macrophages by Nanoparticle-Loaded Escherichia Coli Combined with Immunogenic Cell Death for Cancer Immunotherapy

  • 作者:Wei, B., Pan, J., Yuan, R., Shao, B., Wang, Y., Guo, X. & Zhou, S.
  • 期刊:Nano letters 21, 4231-4240 (2021)
  • 阅读原文


The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Herein, tumor-associated macrophage polarization therapy supplemented with PLGA-DOX (PDOX)-induced ICD is developed for cancer treatment. The nanoparticles/bacteria complex (Ec-PR848) is fabricated for tumor targeting and TAM polarization, and PLGA-R848 (PR848) are attached to the surface of Escherichia coli (E. coli) MG1655 via electrostatic absorption. The toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and E. coli can greatly polarize M2 macrophages to M1 macrophages, while PDOX-induced ICD can also impair the immunosuppression of the tumor microenvironment. This strategy shows that tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapeutic drugs can commendably enhance the efficacy of immunotherapy.