Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, and the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Sci Rep. 2022 Oct 29;12(1):18229. doi: 10.1038/s41598-022-22279-w.
The immune response to radiofrequency ablation (RFA) and cryoablation (CRA) was characterized and compared in a colon cancer mouse model. All studies were conducted under a research protocol approved by the National Institutes of Health, Clinical Center, Animal Care and Use Committee. BALB/cJ mice were inoculated with CT26 cells, and randomized to RFA, CRA, or sham treatment. Mice were sacrificed 3 days post-treatment, and tumor, spleen, and serum were harvested. Cell death was determined by Caspase-3 immunohistochemical and TUNEL stains. Immune response was analyzed using flow cytometry, serum cytokine assay and immunohistochemistry. Cell death, necrosis, and apoptosis induced by ablation were comparable in RFA and CRA. Decreased frequency of systemic T-regulatory cells was found in the CRA group. Both RFA and CRA reduced frequencies of several myeloid-derived suppressor cell (MDSC) subpopulations. RFA induced pro-inflammatory cytokine secretion including TNF-α and IL-12 as well as anti-inflammatory cytokines IL-5, and IL-10. CRA augmented secretion of a wider array of cytokines compared to RFA with both pro- and anti-inflammatory properties including IL-1β, IL-5, IL-6, IL-10, and KC GRO. In the tumor microenvironment, RFA reduced the number of T-regulatory cells, a finding not observed with CRA. Reduction of immune suppression via decreases in T-regulatory cells and MDSC was found to be induced by RFA or CRA. CRA augmented a wider range of cytokines than RFA, which were mainly pro-inflammatory, but also anti-inflammatory. In the tumor microenvironment, RFA demonstrated more pronounced anti-tumoral immunity. Further delineation of specific immunomodulation induced by ablation could inform drug-device development and may play a role in future hypothesis-driven immunomodulatory paradigms that combine immunotherapy drugs with tumor destruction for the treatment of metastatic colon cancer.
射频消融（RFA）和冷冻消融（CRA）的免疫反应在结直肠癌小鼠模型中进行了特征描述和比较。所有研究均在 NIH 临床中心动物护理和使用委员会批准的研究方案下进行。BALB/cJ 小鼠接种 CT26 细胞，随机分为 RFA、CRA 或假处理组。治疗后 3 天处死小鼠，采集肿瘤、脾脏和血清。通过 Caspase-3 免疫组化和 TUNEL 染色检测细胞死亡。使用流式细胞术、血清细胞因子测定和免疫组织化学分析免疫反应。RFA 和 CRA 诱导的细胞死亡、坏死和凋亡相当。在 CRA 组中发现系统性 T 调节细胞的频率降低。RFA 和 CRA 均降低了几种髓源性抑制细胞（MDSC）亚群的频率。RFA 诱导 TNF-α和 IL-12 等促炎细胞因子以及抗炎细胞因子 IL-5 和 IL-10 的分泌。与 RFA 相比，CRA 增强了更广泛的细胞因子分泌，具有促炎和抗炎特性，包括 IL-1β、IL-5、IL-6、IL-10 和 KC GRO。在肿瘤微环境中，RFA 降低了 T 调节细胞的数量，而 CRA 则没有观察到这一现象。通过降低 T 调节细胞和 MDSC 来减少免疫抑制，这在 RFA 或 CRA 中均有发现。与 RFA 相比，CRA 增强了更广泛的细胞因子，主要是促炎细胞因子，但也有抗炎细胞因子。在肿瘤微环境中，RFA 显示出更强的抗肿瘤免疫。对消融诱导的特定免疫调节的进一步描述可以为药物-器械开发提供信息，并可能在未来的免疫调节假设驱动范式中发挥作用，即将免疫治疗药物与肿瘤破坏结合起来，用于治疗转移性结直肠癌。
