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Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles
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Journal Article
Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles
2021
Overview
The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8
+
T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8
+
T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.
Durable response rate to anti-PD-1/PD-L1 therapy remains relatively low in patients with cancer. Here the authors show that metformin-loaded mannose-modified macrophage-derived microparticles reprogram the tumor immune microenvironment and improve responses to anti-PD-1 therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14/19
/ 14/28
/ 38/77
/ 64/60
/ 82/80
/ Animals
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Cell-Derived Microparticles - immunology
/ Collagen
/ Drug Carriers - pharmacology
/ Female
/ Humanities and Social Sciences
/ Humans
/ Immune Checkpoint Inhibitors - pharmacology
/ Immune Checkpoint Inhibitors - therapeutic use
/ Immunity
/ Male
/ Mannose
/ Mice
/ Programmed Cell Death 1 Receptor - antagonists & inhibitors
/ Programmed Cell Death 1 Receptor - immunology
/ Science
/ Therapy
/ Tumor Microenvironment - drug effects
/ Tumor Microenvironment - immunology
/ Tumor-Associated Macrophages - drug effects
/ Tumor-Associated Macrophages - immunology
/ Tumors
