{"title":"Evaluating the Impact of Adjunctive Partial Cryoablation on Dual Checkpoint Inhibitor Immunotherapy Response in a Murine Model.","authors":"Eric Wehrenberg-Klee, Perry Hampilos, Emily E Austin, Bahar Ataeinia, Abigail MacPherson, Thomas LaSalle, Umar Mahmood","doi":"10.1148/rycan.230187","DOIUrl":null,"url":null,"abstract":"<p><p>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%; <i>P</i> < .001). CT-26 mice also had an increased survival rate (57% vs 35%, respectively; <i>P</i> = .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. <b>Keywords:</b> Cancer, Cryoablation, Checkpoint Inhibitor Immunotherapy, Tumor Response <i>Supplemental material is available for this article.</i> © RSNA, 2024.</p>","PeriodicalId":20786,"journal":{"name":"Radiology. Imaging cancer","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiology. Imaging cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1148/rycan.230187","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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%; P < .001). CT-26 mice also had an increased survival rate (57% vs 35%, respectively; P = .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. Keywords: Cancer, Cryoablation, Checkpoint Inhibitor Immunotherapy, Tumor Response Supplemental material is available for this article. © RSNA, 2024.
在小鼠模型中评估辅助性部分冷冻消融对双重检查点抑制剂免疫疗法反应的影响
目的 评估辅助性部分冷冻消融对检查点抑制剂(CPI)免疫疗法反应的影响。材料与方法 对 156 只双植入肿瘤模型小鼠(雌雄数量相等)进行双 CPI 或载体治疗,并随机对单个肿瘤进行部分冷冻消融治疗。冷冻消融后对肿瘤进行 60 天的随访,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化鉴定肿瘤微环境。对不同治疗组的非冷冻消融肿瘤内的 T 细胞浸润和活化特征以及部分消融肿瘤内的细胞因子水平进行了统计比较。此外,还通过免疫荧光对冷冻消融和非冷冻消融肿瘤内的 T 细胞活化情况进行了定性评估。结果 在治疗后 60 天,CPI 和辅助冷冻消融治疗 MC-38 小鼠的存活率(79%)显著高于仅用 CPI 治疗的小鼠(61%;P < .001)。CT-26 小鼠的存活率也有所提高(分别为 57% 对 35%;P = .04)。冷冻消融后,观察到治疗肿瘤内的炎性细胞因子和趋化因子增加。非冷冻消融肿瘤的流式细胞术显示 CD8 T 细胞活化增加。冷冻消融后的免疫荧光和组织学评估进一步显示了强大的 CD8 T 细胞和髓细胞浸润。结论 在多种癌症模型中,无论是部分消融还是远处(未消融)肿瘤部位,辅助低温消融都能显著提高对双 CPI 的反应。免疫分析表明,低温消融可促进部分低温消融肿瘤内的强烈免疫反应,从而增强远处肿瘤部位适应性免疫系统的活化。关键词癌症 低温消融 检查点抑制剂免疫疗法 肿瘤反应 本文有补充材料。© RSNA, 2024.
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