Summary

Background: Radiation therapy (RT) has demonstrated ability to augment antitumor immunity, promoting immunogenic cell death (ICD) and stimulating immune adjuvant effects. On the other hand, RT has also been reported to induce immunosuppressive responses. A new class of material with high electron density, hafnium oxide, was designed at the nanoscale (HfO2-NP) to efficiently absorb ionizing radiation and augment the radiation dose
deposited from within the tumor cells. […]

Methods: The potential ability of HfO2-NP exposed to RT to transform tumors into immunologically active lesions was tested in vitro and in vivo. In vitro, the level of ICD markers was evaluated in a panel of human cancer cell lines, following cells treated or not with HfO2-NP and irradiated. In vivo, a vaccination assay was performed to evaluate the host immune responses in immunocompetent mice inoculated with murine CT26 cancer cells treated or not with HfO2-NP and irradiated with 6 Gy. […]

Results: Higher DAMPs levels (cell surface expression of calreticulin, extracellular adenosine triphosphate level and extracellular high-mobility group box 1 level) were observed in the tested cancer cells treated with HfO2-NP + RT when compared to cancer cells exposed to RT. […]

Conclusions: These results suggest an efficient cell killing (ability to generate ICD) with superior potential of HfO2-NP + RT to transform the tumor into an effective in situ vaccine when compared to RT. Moreover, HfO2-NP treatment generates a marked increase of immune cells infiltration in the tumors suggesting that it may convert immunologically “cold” tumor into “hot” tumor and could be combined with immunotherapeutic agents across oncology.