Radiotherapy-Activated Hafnium Oxide Nanoparticles Produce Abscopal Effect in a Mouse Colorectal Cancer Model
| Autor: | Ping Zhang, Audrey Darmon, Naeemunnisa Mohamed Anesary, Sébastien Paris, Julie Marill |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Colorectal cancer
Lymphocyte medicine.medical_treatment Biophysics Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials Immune system Drug Discovery Medicine Cytotoxic T cell business.industry Organic Chemistry Abscopal effect General Medicine 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Radiation therapy medicine.anatomical_structure Cancer cell Cancer research 0210 nano-technology business CD8 |
| Zdroj: | International Journal of Nanomedicine. 15:3843-3850 |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s250490 |
| Popis: | Purpose Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare. Methods Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model. Results We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells. Conclusion These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy. |
| Databáze: | OpenAIRE |
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