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07-12-2022 | Melanoma | Research

Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma

Authors: Ami Nishikawa, Yutaro Suzuki, Masahiro Kaneko, Akira Ito

Published in: Cancer Immunology, Immunotherapy | Issue 6/2023

Abstract

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors.

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Title: Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma
Authors: Ami Nishikawa
Yutaro Suzuki
Masahiro Kaneko
Akira Ito
Publication date: 07-12-2022
Publisher: Springer Berlin Heidelberg
Keywords: Melanoma
Melanoma
Immunomodulator
Checkpoint Inhibitors
Published in: Cancer Immunology, Immunotherapy / Issue 6/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-022-03345-8

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