Progress on Modulating Tumor‐Associated Macrophages with Biomaterials

Sylvestre, Meilyn; Crane, Courtney A.; Pun, Suzie H.

doi:10.1002/adma.201902007

Cited by 129 publications

(124 citation statements)

References 155 publications

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“…[10,11] Of note, the plastic phenotype of TAM can change in response to the TME into M1 type with antigenpresenting ability and upregulation of the inflammatory cytokines expression. Aiming at the TAMs in the TME, [12] the nanotechnology-based drug delivery systems can be used to achieve immune adjuvant therapy for cancer, [13][14][15][16][17] which can be used as an alternative method instead of directly targeting tumor cells. The drug selection and research are ongoing in early clinical trials currently.…”

Section: The Progress Of Antitumor Immunotherapy Is Usually Limited Bmentioning

confidence: 99%

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Liu

Wang

Guo

et al. 2020

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The progress of antitumor immunotherapy is usually limited by tumor‐associated macrophages (TAMs) that account for the highest proportion of immunosuppressive cells in the tumor microenvironment, and the TAMs can also be reversed by modulating the M2‐like phenotype. Herein, a biomimetic polymer magnetic nanocarrier is developed with selectively targeting and polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier PLGA‐ION‐R837 @ M (PIR @ M) is achieved, first, by the fabrication of magnetic polymer nanoparticles (NPs) encapsulating Fe3O4 NPs and Toll‐like receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of the lipopolysaccharide (LPS)‐ treated macrophage membranes on the surface of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy of Fe3O4 NPs and R837. The relevant mechanism of the polarization is deeply studied through analyzing the mRNA expression of the signaling pathways. Different from previous reports, the polarization is ascribed to the fact that Fe3O4 NPs mainly activate the IRF5 signaling pathway via iron ions instead of the reactive oxygen species‐induced NF‐κB signaling pathway. The anticancer effect can be effectively enhanced through potentiating immunotherapy by the polarization of the TAMs in the combination of Fe3O4 NPs and R837.

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Section: The Progress Of Antitumor Immunotherapy Is Usually Limited Bmentioning

confidence: 99%

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Liu

Wang

Guo

et al. 2020

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“…This could be achieved, for example, by enhancing negative regulation of TLR signaling and silent clearance of apoptotic cells (33,(355)(356)(357)(358)(359), as well as by augmenting IL-10 receptor signaling (360)(361)(362). To note, thanks to their high phagocytic capacity, targeting intestinal Mfs could be facilitated by "delivery systems" such as nanomaterials and biomaterials (363), as has been shown in mouse model of organ transplantation (364).…”

Section: Monocytes and Macrophagesmentioning

confidence: 99%

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Caër

Wick

2020

Front. Immunol.

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Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex immune-mediated disease of the gastrointestinal tract that increases morbidity and negatively influences the quality of life. Intestinal mononuclear phagocytes (MNPs) have a crucial role in maintaining epithelial barrier integrity while controlling pathogen invasion by activating an appropriate immune response. However, in genetically predisposed individuals, uncontrolled immune activation to intestinal flora is thought to underlie the chronic mucosal inflammation that can ultimately result in IBD. Thus, MNPs are involved in fine-tuning mucosal immune system responsiveness and have a critical role in maintaining homeostasis or, potentially, the emergence of IBD. MNPs include monocytes, macrophages and dendritic cells, which are functionally diverse but highly complementary. Despite their crucial role in maintaining intestinal homeostasis, specific functions of human MNP subsets are poorly understood, especially during diseases such as IBD. Here we review the current understanding of MNP ontogeny, as well as the recently identified human intestinal MNP subsets, and discuss their role in health and IBD.

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“… 43 Furthermore, in order to specifically target TAMs rather than other cells, TAM-mediated endocytosis that is triggered by ligand-receptor interaction becomes a new target option. 44 Among them, the mannose receptor (MR) is highly expressed on the surface of M2-like TAMs that can efficiently induce internalization. In view of this, Huang et al design one nanoparticle that possesses an affinity for MR on TAMs and can respond to the low pH in TME.…”

Section: Discussionmentioning

confidence: 99%

Targeted delivery of miR-99b reprograms tumor-associated macrophage phenotype leading to tumor regression

Wang

Zhao

et al. 2020

J Immunother Cancer

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BackgroundAccumulating evidence has shown that tumor-associated macrophages (TAMs) play a critical role in tumor progression. Targeting TAMs is a potential strategy for tumor immunotherapy. However, the mechanism underlying the TAM phenotype and function needs to be resolved. Our previous studies have demonstrated that miR-125a can reverse the TAM phenotype toward antitumor. Meanwhile, we have found that miR-125a and miR-99b cluster in the first intron of the same host gene, and are transcribed simultaneously in bone marrow-derived macrophages (BMDMs) following LPS+IFNγ stimulation. However, it remains unclear whether miR-99b by itself can exert an antitumor effect by regulating macrophage phenotype.MethodsmiR-99b and/or miR-125a were delivered into TAMs of orthotopic hepatocellular carcinoma (HCC) or subcutaneous Lewis lung cancer (LLC) mice. The effect of treatment was evaluated by live imaging, TUNEL staining and survival tests. The phenotype of the immune cells was determined by qRT-PCR, ELISA, western blot and FACS. The capability of miR-99b-mediated macrophage phagocytosis and antigen presentation was detected by FACS and immunofluorescence staining. The underlying molecular mechanism was examined by qRT-PCR, reporter assay and western blot, and further verified in the tumor model. The expression of miR-99b and its target genes was determined in TAMs sorted from tumor and adjacent tissues in patients with liver cancer.ResultsTargeted delivery of miR-99b and/or miR-125a into TAMs significantly impeded the growth of HCC and LLC, especially after miR-99b delivery. More importantly, the delivery of miR-99b re-educated TAM toward antitumor phenotype with enhanced immune surveillance. Further investigation of mechanisms showed that macrophage-specific overexpression of miR-99b promoted M1 while suppressing M2 macrophage polarization by targeting κB-Ras2 and/or mTOR, respectively. miR-99b-overexpressed M1 macrophage was characterized by stronger capability of phagocytosis and antigen presentation. Additionally, delivery of simTOR or siκB-Ras2 into TAMs inhibited miR-99b antagomir-triggered tumor growth. Finally, miR-99b expression was lower in TAMs of patients with liver cancer than that in adjacent tissues, while the expression of κB-Ras2 and mTOR was reversed.ConclusionsOur results reveal the mechanism of miR-99b-mediated TAM phenotype, indicating that TAM-targeted delivery of miR-99b is a potential strategy for cancer immunotherapy.

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Progress on Modulating Tumor‐Associated Macrophages with Biomaterials

Cited by 129 publications

References 155 publications

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Targeted delivery of miR-99b reprograms tumor-associated macrophage phenotype leading to tumor regression

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