Abstract:
:Myeloid-derived suppressor cells (MDSC) are innate immune cells that potently inhibit T cells. In cancer, novel therapies aimed to activate T cells can be rendered ineffective due to the activity of MDSCs. Thus, targeted inhibition of MDSCs may greatly enhance T-cell-mediated antitumor immunity, but mechanisms remain obscure. Here we show, for the first time, that scavenger receptor type B-1 (SCARB1), a high-affinity receptor for spherical high-density lipoprotein (HDL), is expressed by MDSCs. Furthermore, we demonstrate that SCARB1 is specifically targeted by synthetic high-density lipoprotein-like nanoparticles (HDL NP), which reduce MDSC activity. Using in vitro T-cell proliferation assays, data show that HDL NPs specifically bind SCARB1 to inhibit MDSC activity. In murine cancer models, HDL NP treatment significantly reduces tumor growth, metastatic tumor burden, and increases survival due to enhanced adaptive immunity. Flow cytometry and IHC demonstrate that HDL NP-mediated suppression of MDSCs increased CD8+ T cells and reduced Treg cells in the metastatic tumor microenvironment. Using transgenic mice lacking SCARB1, in vivo data clearly show that the HDL NPs specifically target this receptor for suppressing MDSCs. Ultimately, our data provide a new mechanism and targeted therapy, HDL NPs, to modulate a critical innate immune cell checkpoint to enhance the immune response to cancer. Mol Cancer Ther; 17(3); 686-97. ©2017 AACR.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Plebanek MP,Bhaumik D,Bryce PJ,Thaxton CSdoi
10.1158/1535-7163.MCT-17-0981subject
Has Abstractpub_date
2018-03-01 00:00:00pages
686-697issue
3eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-17-0981journal_volume
17pub_type
杂志文章abstract::The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables ac...
journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0689
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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