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Anti-tumor immune responses of tumor-associated macrophages via toll-like receptor 4 triggered by cationic polymers

Paper ID Volume ID Publish Year Pages File Format Full-Text
6852 522 2013 10 PDF Available
Title
Anti-tumor immune responses of tumor-associated macrophages via toll-like receptor 4 triggered by cationic polymers
Abstract

Agonists of toll-like receptors (TLRs) are potential therapeutic reagents for cancer immunotherapy. Cationic polymers such as polyethyleneimine (PEI) with nucleic acid drug delivery capability are approved for use in clinical trials, and recent reports indicate that these cationic polymers have significant immunological activity mediated by TLRs. In the present study, we demonstrated that cationic polymers such as PEI and cationic dextran could reverse tumor-associated macrophages (TAMs) polarization and promote IL-12 expression both in vitro and in vivo. The stimulatory role of cationic polymers was remarkably attenuated in TAMs pre-treated with TLR-4 blocking antibody or TAMs from TLR-4 knockout mice. Additionally, these cationic polymers exerted direct tumoricidal activity by promoting Th 1 and NK cell infiltration, suppressing tumor angiogenesis and prolonging the survival of sarcoma-bearing wild-type. These phenomena were abrogated in TLR-4 knockout mice, suggesting that the immune stimulation was primarily mediated by TLR-4. In conclusion, these results demonstrated that cationic polymers could transform the immunotolerogenic phenotype of TAMs through TLR-4 signaling, thereby promoting therapeutic anti-tumor immunity. Our present study suggests a new class of drugs as a candidate for future cancer immunotherapy.

Keywords
Cationic polymers; Tumor-associated macrophage; Toll-like receptor 4; Cancer immunotherapy
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Anti-tumor immune responses of tumor-associated macrophages via toll-like receptor 4 triggered by cationic polymers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 3, January 2013, Pages 746–755
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us