From the Department of Radiology, Center for Precision Imaging, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St, Rm 5.407, Charlestown, MA 02129 (E.W.K., P.H., E.E.A., B.A., A.M., T.L., U.M.); and Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital, Boston, Mass (E.W.K., P.H.).
Radiol Imaging Cancer. 2024 Nov;6(6):e230187. doi: 10.1148/rycan.230187.
Purpose To evaluate the impact of adjunctive partial cryoablation on checkpoint inhibitor (CPI) immunotherapy response. Materials and Methods One hundred fifty-six mice (equal number of male and female animals) with dual-implanted tumor models were treated with dual CPI or a vehicle and randomized to treatment of a single tumor with partial cryoablation. Tumors were followed for 60 days following cryoablation for response assessment. In additional groups, the tumor microenvironment was characterized via flow cytometry, cytokine analysis, and immunohistochemistry. Statistical comparison was made between the different treatment groups regarding T-cell infiltration and activation characteristics within the noncryoablated tumor and cytokine levels within the partially ablated tumor. Additionally, qualitative assessment of T-cell activation within the cryoablated and noncryoablated tumors at immunofluorescence was carried out. Results At 60 days following treatment, CPI and adjunctive cryoablation-treated MC-38 mice had a significantly increased survival rate (79%) compared with mice treated with CPI alone (61%; < .001). CT-26 mice also had an increased survival rate (57% vs 35%, respectively; = .04). Following cryoablation, increases in inflammatory cytokines and chemokines within the treated tumors were observed. Flow cytometry of noncryoablated tumor showed increased CD8 T-cell activation. Immunofluorescence and histologic evaluation following cryoablation further demonstrated a robust CD8 T-cell and myeloid infiltrate. Conclusion Adjunctive cryoablation significantly increased the response to dual CPI in multiple cancer models at both partially ablated and distant (nonablated) tumor sites. Immune analysis suggests cryoablation promotes a vigorous immune response within the partially cryoablated tumor that increases activation of the adaptive immune system within distant tumor sites. Cancer, Cryoablation, Checkpoint Inhibitor Immunotherapy, Tumor Response © RSNA, 2024.
目的 评估辅助部分冷冻消融对检查点抑制剂（CPI）免疫治疗反应的影响。
材料与方法 156 只植入了双肿瘤模型的小鼠（雌雄动物数量相等）接受了双重 CPI 或载体治疗，并随机分为接受单一肿瘤部分冷冻消融治疗的两组。在冷冻消融后 60 天内对肿瘤进行随访，以评估反应。在其他组中，通过流式细胞术、细胞因子分析和免疫组织化学对肿瘤微环境进行了特征描述。对不同治疗组的非冷冻消融肿瘤内 T 细胞浸润和激活特征以及部分消融肿瘤内细胞因子水平进行了统计学比较。此外，还对冷冻消融和非冷冻消融肿瘤内 T 细胞激活的免疫荧光定性评估进行了分析。
结果 治疗后 60 天，接受 CPI 和辅助冷冻消融治疗的 MC-38 小鼠的生存率（79%）明显高于单独接受 CPI 治疗的小鼠（61%；<.001）。CT-26 小鼠的生存率也有所提高（分别为 57%和 35%；=.04）。冷冻消融后，观察到治疗肿瘤内炎症细胞因子和趋化因子水平升高。非冷冻消融肿瘤的流式细胞术显示 CD8 T 细胞激活增加。冷冻消融后的免疫荧光和组织学评估进一步证明了强大的 CD8 T 细胞和髓样细胞浸润。
结论 辅助冷冻消融术在多个肿瘤模型中均显著提高了双重 CPI 的反应率，包括部分消融和远处（未消融）肿瘤部位。免疫分析表明，冷冻消融术在部分冷冻消融肿瘤中促进了强烈的免疫反应，增加了远处肿瘤部位适应性免疫系统的激活。
癌症，冷冻消融，检查点抑制剂免疫治疗，肿瘤反应
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