Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models.

Hydrogen peroxide (H ₂ O ₂ ) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H ₂ O ₂ and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H ₂ O ₂ on antitumor immunity remain unclear. To investigate the effects of H ₂ O ₂ , especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H ₂ O ₂ mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H ₂ O ₂ /RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H ₂ O ₂ or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H ₂ O ₂ /RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8 ⁺ (cluster of differentiation 8) T cells and the frequency of IFN-γ ⁺ (interferon gamma) CD8 ⁺ T cells were higher in the noninjected/nonirradiated tumors in the H ₂ O ₂ /RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H ₂ O ₂ /RT group. Intratumoral injection of H ₂ O ₂ combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H ₂ O ₂ /RT therapy combined with cancer immunotherapies, even for advanced cancers.
(© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)