Abstract:
:Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis. The macropinocytic uptake of nab-paclitaxel induced macrophage immunostimulatory (M1) cytokine expression and synergized with IFNγ to promote inducible nitric oxide synthase expression in a TLR4-dependent manner. Nab-paclitaxel was internalized by tumor-associated macrophages in vivo, and therapeutic doses of nab-paclitaxel alone, and in combination with gemcitabine, increased the MHCII+CD80+CD86+ M1 macrophage population. These data revealed an unanticipated role for nab-paclitaxel in macrophage activation and rationalized its potential use to target immune evasion in pancreatic cancer. Cancer Immunol Res; 5(3); 182-90. ©2017 AACR.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Cullis J,Siolas D,Avanzi A,Barui S,Maitra A,Bar-Sagi Ddoi
10.1158/2326-6066.CIR-16-0125subject
Has Abstractpub_date
2017-03-01 00:00:00pages
182-190issue
3eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-16-0125journal_volume
5pub_type
杂志文章abstract::Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages triggered PMT in glioma stem cells (GSC) via small extracellular ...
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pub_type: 临床试验,杂志文章
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更新日期:2015-05-01 00:00:00
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journal_title:Cancer immunology research
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doi:10.1158/2326-6066.CIR-16-0400
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journal_title:Cancer immunology research
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
pub_type: 杂志文章
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journal_title:Cancer immunology research
pub_type: 杂志文章
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journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0182
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journal_title:Cancer immunology research
pub_type: 杂志文章,评审
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
pub_type: 杂志文章
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更新日期:2017-12-01 00:00:00
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pub_type: 杂志文章
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