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Updated: Nov 15, 2025

A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research
Published on: August 15, 2019
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.
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.
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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