Depleting tumor-associated Tregs via nanoparticle-mediated hyperthermia to enhance anti-CTLA-4 immunotherapy
| Autor: | Hongwei Chen, Alfred E. Chang, Hayley J. Paholak, Nicholas O. Stevers, Kanokwan Sansanaphongpricha, Qiao Li, Joseph Burnett, Duxin Sun, Xin Luan, Miao He |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Hyperthermia
Combination therapy medicine.medical_treatment Population Biomedical Engineering Medicine (miscellaneous) Breast Neoplasms Bioengineering CD8-Positive T-Lymphocytes Development Ferric Compounds T-Lymphocytes Regulatory Flow cytometry Mice 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Immune Tolerance Tumor Microenvironment Animals Humans Medicine CTLA-4 Antigen General Materials Science education 030304 developmental biology 0303 health sciences education.field_of_study Tumor microenvironment medicine.diagnostic_test business.industry Hyperthermia Induced Immunotherapy Phototherapy medicine.disease Combined Modality Therapy Blockade Disease Models Animal 030220 oncology & carcinogenesis Cancer research Nanoparticles Female business Research Article |
| Zdroj: | Nanomedicine (Lond) |
| ISSN: | 1748-6963 1743-5889 |
| DOI: | 10.2217/nnm-2019-0190 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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