期刊
NANOMEDICINE
卷 15, 期 1, 页码 77-92出版社
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2019-0190
关键词
anti-CTLA-4 immunotherapy; immunosuppression; photothermal therapy; Tregs; tumor microenvironment
资金
- University of Michigan Comprehensive Cancer Center grant [NIH 2P30CA046592-24]
- Upjohn Research Award [G021782]
- UMOR Award [29208]
- MCubed Award [U064006]
- Gillson Longenbaugh Foundation
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] .
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