Table 3 Studies that investigated the effects of combining cryoablation with immunomodulation and their results
From: Immuno-thermal ablations – boosting the anticancer immune response
Cryoablation and Immunotherapy | |||||
|---|---|---|---|---|---|
Reference | Tumor Model | Immunotherapy | Endpoint | Ablation Monotherapy | Combination Therapy |
den Brok, M.H., et al. [12] | B16OVA Murine Melanoma | CpG | Total Number of Dendritic Cells per Lymph Node 2 Days After Treatment | No Significance Established Versus Control | Significantly Increased Versus Monotherapy (p < 0.05) |
CD80 Expression on OVA Specific Dendritic Cells 2 Days After Treatment | Significantly Increased Versus Control (p < 0.05) | Significantly Increased Compared to Monotherapy (p < 0.05) | |||
MHC Class I Presentation (B3Z Activation) | No Significance Established Versus Control | Significantly Increased Versus Monotherapy (p < 0.05) | |||
MHC Class II Presentation (IL-2 Production) | Significantly Increased Versus Control (p < 0.05) | Significantly Increased Versus Monotherapy (p < 0.05) | |||
OVA Rechallenge to Animals Surviving 40 Days | Significantly Increased Survival Versus Control (p < 0.005) | Complete Protection Against Tumor Outgrowth (p < 0.005) | |||
Survival From Contralateral Metastasis | No Significance Established Versus Control | Significantly Prolonged Versus Monotherapy (p < 0.005) | |||
Local Recurrence Within 15 Days | Significantly Higher Recurrence Versus Combination Therapy (p < 0.05) | Complete Protection Against Outgrowth of Local Recurrences | |||
Machlenkin, A. [37] | 3LL Murine Lewis Lung Carcinoma & B16OVA Murine Melanoma | Intratumoral Injection of Immature Dendritic Cells | Survival Following Amputation of Foot Bearing Primary Tumor | No Significance Established Versus Control | Significantly Prolonged Versus Monotherapy (p = 0.005) |
Proliferation of Tumor Specific CD8+ T Cells | 35% of CD8+ T Cells Underwent Division | 65% of CD8+ T Cells Underwent Division | |||
Rechallenge With Malignant Cells to Animals Surviving 60 Days | No Significance Established Versus Control | Significantly Prolonged Survival Versus Monotherapy (p = 0.029) | |||
Redondo, P., et al. [11] | B16OVA Murine Melanoma | Topical TLR-7 Agonist Imiquimod | Rechallenge With Malignant Cells to Animals Surviving 15 Days | Significantly Delayed the Outgrowth of Secondary Tumors Compared to Control (p < 0.0001) | Significantly Protection Against Secondary Tumor Outgrowth Compared to Monotherapy (p < 0.0001) |
Waitz, R., et al. [15] | TRAMP C2 Murine Prostate Cancer | Ipilumimab CTLA-4 Inhibition | Tumor Free Survival | No Significance Established Versus Control | Significantly Prolonged Versus Monotherapy (p < 0.0005) |
Challenge With Secondary Tumor After 1 Day | 0 out of 5 Mice Rejected the Secondary Tumor | 4 out of 9 Mice Rejected the Secondary Tumor | |||
Number of Infiltrating CD4+ T Cells After 15 Days | No Significance Established Versus Control | Significantly Increased Versus Control Only (p = 0.01–0.05) | |||
Number of Infiltrating CD8+ T Cells After 15 Days | No Significance Established Versus Control | Significantly Increased Versus Monotherapy (p < 0.001) | |||
Ratio of Intratumoral CD4+ Effector T cells to FoxP3 Regulatory T cells | No Significance Established Versus Control | Significantly Increased Versus Monotherapy (p < 0.001) | |||
Ratio of Intratumoral CD8+ Effector T cells to FoxP3 Regulatory T cells | No Significance Established Versus Control | Significantly Increased Versus Monotherapy (p = 0.001) | |||
Levy, M.Y., et al. [44] | CT26 Murine Colon Cancer | Cyclophosphamide | Total Survival After Inoculation | Significance Not Established Versus Control (p = 0.46) | Significantly Prolonged Versus Monotherapy (p < 0.0001) |
Rechallenge With Malignant Cells to Animals Surviving 150 Days | No Significance Established Versus Control | Significantly Prolonged Survival Versus Controls (p = 0.0051) | |||
den Brok, M.H., et al. [10] | B16OVA Murine Melanoma | Anti-CTLA-4 Antibodies | OVA Rechallenge to Animals Surviving 40 Days | Used as Control with Sham IgG Antibodies | Significant Increase in Percentage Survival Versus Control (p < 0.05) |
OVA kb Tetramer Positive CD8b + T Cells After 10 Days | 0.1% of CD8b + T Cells | 5.8% of CD8b + T Cells | |||
Anti-CD25 Antibodies | OVA Rechallenge to Animals Surviving 40 Days | Used as Control with Sham IgG Antibodies | Significant Increase in Percentage Survival Versus Control (p < 0.05) | ||
OVA kb Tetramer Positive CD8b + T Cells After 10 Days | 0.1% of CD8b + T Cells | 5.0% of CD8b + T Cells | |||