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

Int J Mol Sci. 2021 Feb 17;22(4):1973. doi: 10.3390/ijms22041973.

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.

Keywords: abscopal effect; frozen autograft; tumor; tumor-suppressive effect.

MeSH terms

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

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor