hafnia and Colorectal-Neoplasms

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.. 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.. 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.. 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.

Topics: Animals; Antineoplastic Agents, Immunological; Biological Availability; CD8-Positive T-Lymphocytes; Colorectal Neoplasms; Female; Hafnium; Metal Nanoparticles; Mice, Inbred BALB C; Neoplasms, Experimental; Oxides

The cGAS-STING pathway can be activated by radiation induced DNA damage and because of its important role in anti-cancer immunity activation, methods to increase its activation in cancer cells could provide significant therapeutic benefits for patients. We explored the impact of hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy on cell death, DNA damage, and activation of the cGAS-STING pathway. We demonstrate that NBTXR3 activated by radiotherapy enhances cell destruction, DNA double strand breaks, micronuclei formation and cGAS-STING pathway activation in a human colorectal cancer model, compared to radiotherapy alone.

Topics: Colorectal Neoplasms; DNA Damage; Hafnium; HCT116 Cells; Humans; Membrane Proteins; Nanoparticles; Nucleotidyltransferases; Oxides; Signal Transduction