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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