Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer.
Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer.
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微波消融联合 OK-432 在乳腺癌小鼠模型中诱导 Th1 型反应和特异性抗肿瘤免疫。
DOI：
10.1186/s12967-017-1124-9
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发表时间：
2017-01-31
影响因子：
7.4
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Li L;Wang W;Pan H;Ma G;Shi X;Xie H;Liu X;Ding Q;Zhou W;Wang S
背景微波消融（MWA）等微创治疗方法广泛应用于实体瘤的治疗。以往的研究表明微波消融治疗小乳腺癌是可行的，热消融可能诱导适应性抗肿瘤免疫。然而，诱导的免疫应答大多较弱，MWA在乳腺癌中的免疫调节作用尚不清楚。免疫刺激剂OK-432可以诱导肿瘤特异性T细胞反应，并可能增强MWA.MethodsWe治疗4 T1乳腺癌荷瘤BALB/c小鼠MWA，OK-432，MWA + OK-432，或离开没有治疗。采用Kaplan-Meyer法评估生存时间，并通过对数秩检验比较生存曲线。在消融后第25天，存活小鼠接受肿瘤再激发，每5天计算再激发肿瘤体积。采用免疫组化和流式细胞术检测消融组织和脾脏中T细胞免疫反应。用酶联免疫斑点法检测肿瘤特异性免疫反应。此外，从酶联免疫吸附试验（ELISA）中确定细胞因子模式。结果微波消融加OK-432导致比单次治疗更长的生存期，并保护大多数存活的小鼠免受肿瘤再攻击。局部和全身T细胞应答均由MWA诱导，并通过随后施用OK-432进一步增强。此外，MWA和OK-432的组合比单独MWA诱导更强的肿瘤特异性免疫应答。此外，OK-432和MWA协同促进Th 1型，但不是Th 2型细胞因子的生产，和极化T细胞反应的Th 1-优势state.ConclusionsThe T细胞免疫反应激活MWA在乳腺癌。MWA与OK-432联合应用可诱导Th 1型免疫应答，并诱导特异性抗肿瘤免疫。
BackgroundMinimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.MethodsWe treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan–Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.ResultsMicrowave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.ConclusionsThe T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.