Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a

Noritaka Yonezawa1, Hideki Murakami2, Satoru Demura1

  • 1Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

Insights

Re-implantation of frozen bone grafts showed an abscopal effect, inhibiting tumor growth. Anti-programmed death-1 (PD-1) therapy demonstrated a more potent abscopal effect, enhancing anti-tumor immunity.

Area of Science:

  • Oncology
  • Immunology
  • Orthopedics

Background:

  • The abscopal effect, a phenomenon where localized cancer treatment induces systemic anti-tumor immunity, is of significant interest.
  • Investigating novel therapeutic strategies to enhance the abscopal effect is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To evaluate the abscopal effect of re-implanting liquid nitrogen-treated tumor-bearing bone grafts.
  • To assess the synergistic effect of anti-programmed death-1 (PD-1) therapy in combination with cryotreatment for bone metastases.

Main Methods:

  • A bone metastasis model was established in C3H mice by injecting MMT-060562 cells into the tibiae.
  • Tumors were treated with excision, liquid nitrogen cryotreatment, or a combination with anti-PD-1 antibody therapy.
  • The abscopal effect was quantified by measuring the growth inhibition of non-treated, contralateral tumors and assessing immune cell infiltration.

Main Results:

  • Re-implantation of frozen autografts significantly inhibited abscopal tumor growth.
  • Anti-PD-1 antibody treatment demonstrated a more potent abscopal effect compared to cryotreatment alone.
  • Anti-PD-1 therapy significantly increased CD8+ T cell infiltration and interferon-γ production in spleen cells.

Conclusions:

  • Re-implantation of tumor-bearing frozen autografts can induce an abscopal effect.
  • Anti-PD-1 therapy is a promising strategy to enhance the abscopal effect and anti-tumor immunity in bone metastases.
  • Liquid nitrogen-treated bone grafts alone did not elicit a strong T-cell response or significant tumor suppression.

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