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.
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