Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model.

Abstract

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6-8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.

• Authors: Noritaka Yonezawa, Hideki Murakami, Satoru Demura, Satoshi Kato, Shinji Miwa, Katsuhito Yoshioka, Kazuya Shinmura, Noriaki Yokogawa, Takaki Shimizu, Norihiro Oku, Ryo Kitagawa, Makoto Handa, Ryohei Annen, Yuki Kurokawa, Kazumi Fushimi, Eishiro Mizukoshi, Hiroyuki Tsuchiya
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 4 (Feb 17 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33671258 (Publication Type: Journal Article)

Chemical References

• Immune Checkpoint Inhibitors
• Programmed Cell Death 1 Receptor

Topics

• Animals
• Autografts (drug effects)
• Bone Neoplasms (drug therapy, immunology, pathology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinogenesis (pathology)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Female
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Mice, Inbred C3H
• Neoplasm Metastasis
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, metabolism)
• Splenomegaly (pathology)
• Tumor Burden (drug effects)
• Mice