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Depleting tumor-associated Tregs via nanoparticle-mediated hyperthermia to enhance anti-CTLA-4 immunotherapy
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Document Title
Depleting tumor-associated Tregs via nanoparticle-mediated hyperthermia to enhance anti-CTLA-4 immunotherapy
Author
Chen HW, Luan X, Paholak HJ, Burnett JP, Stevers NO, Sansanaphongpricha K, He M, Chang AE, Li Q, Sun DX
Name from Authors Collection
Affiliations
University of Michigan System; University of Michigan; National Science & Technology Development Agency - Thailand; National Nanotechnology Center (NANOTEC); University of Michigan System; University of Michigan
Type
Article
Source Title
NANOMEDICINE
ISSN
1743-5889
Year
2020
Volume
15
Issue
21
Open Access
Green Published
Publisher
FUTURE MEDICINE LTD
DOI
10.2217/nnm-2019-0190
Format
Abstract
Aim: We aim to demonstrate that a local nanoparticle-mediated hyperthermia can effectively eliminate tumor-associated Tregs and thereby boost checkpoint blockade-based immunotherapy. Materials & methods: Photothermal therapy (PTT), mediated with systemically administered stealthy iron-oxide nanoparticles, was applied to treat BALB/c mice bearing 4T1 murine breast tumors. Flow cytometry was applied to evaluate both Treg and CD8(+) T-cell population. Tumor growth following combination therapy of both PTT and anti-CTLA-4 was further evaluated. Results: Our data reveal that tumor-associated Tregs can be preferentially depleted via iron-oxide nanoparticles-mediated PTT. When combining PTT with anti-CTLA-4 immunotherapy, we demonstrate a significant inhibition of syngeneic 4T1 tumor growth. Conclusion: This study offers a novel strategy to overcome Treg-mediated immunosuppression and thereby to boost cancer immunotherapy. [GRAPHICS] .
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
University of Michigan Comprehensive Cancer Center grant [NIH 2P30CA046592-24]; Upjohn Research Award [G021782]; UMOR Award [29208]; MCubed Award [U064006]; Gillson Longenbaugh Foundation
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Publication Source
WOS