不同热剂量等级的微波消融治疗对结肠癌小鼠T细胞的影响
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摘要
目的:探讨不同热剂量等级的微波消融治疗对诱发结肠癌小鼠T细胞的影响。方法:建立荷瘤小鼠的结肠癌MC38模型,分为对照组和微波消融组,根据热剂量等级将微波消融组分为低(5 W、60 s),中(10 W、60 s),高(15 W、60 s)剂量组。于荷瘤9 d时,给予微波消融治疗,观察小鼠的肿瘤生长情况。给予微波消融处理后14 d,取小鼠脾脏研磨制成单细胞悬液,用流式细胞术检测脾脏中的CD3~+T、CD4~+T、CD8~+T细胞。结果:与对照组相比,各微波消融组小鼠的肿瘤体积明显缩小(P<0.05),高、中、低剂量组的CD3~+T、CD4~+T细胞均明显高于对照组(P<0.05或P<0.01),高剂量组明显高于中、低剂量组(P<0.05)。高剂量组的CD4~+/CD8~+T细胞比值明显高于中、低剂量组(P<0.05),且与对照组相比,增高显著(P<0.01)。四组间的CD8~+T细胞不存在统计学差异(P>0.05)。结论:微波消融能增强小鼠的免疫功能,高剂量效果更好。
Objective: To investigate the effect of microwave ablation with different thermal dosages on T cells in mice with colon cancer. Methods: MC38 colon cancer models of tumor-bearing mice were established and thereafter,randomized to the the control group and microwave ablation group,which were divided into low( 5 W,60 s),moderate( 10 W,60 s),and high( 15 W,60 s) dose groups. On the 9 th day after colon tumor cells implantation,the mice underwent the microwave and the tumor growth were observed. On 14 th day of microwave ablation,CD3~+T,CD4~+T,and CD8~+T cells in the spleens of mice were collected and detected by flow cytometry. Results: The tumor volumes of mice in microwave ablation groups were decreased compared with those in the control group( P < 0. 05). The percentages of CD3~+T,CD4~+T cells in spleens of mice in microwave ablation groups were significantly increased versus those in control group( P < 0. 05 or P < 0. 01),especially in the high dose group( P < 0. 05). Further,the percentages of CD4~+/CD8~+T cells in spleens of mice in high dose group was elevated versus those in moderate dose group and low dose group( P < 0. 05),as well as the control group( P < 0. 01). The percentages of CD8~+T cells were insignificant in each group( P > 0. 05). Conclusion: Microwave ablation can activate the immune functionality and inhibit the tumor growth in mice with colon cancer,and higher dose,more effective.
Objective: To investigate the effect of microwave ablation with different thermal dosages on T cells in mice with colon cancer. Methods: MC38 colon cancer models of tumor-bearing mice were established and thereafter,randomized to the the control group and microwave ablation group,which were divided into low( 5 W,60 s),moderate( 10 W,60 s),and high( 15 W,60 s) dose groups. On the 9 th day after colon tumor cells implantation,the mice underwent the microwave and the tumor growth were observed. On 14 th day of microwave ablation,CD3~+T,CD4~+T,and CD8~+T cells in the spleens of mice were collected and detected by flow cytometry. Results: The tumor volumes of mice in microwave ablation groups were decreased compared with those in the control group( P < 0. 05). The percentages of CD3~+T,CD4~+T cells in spleens of mice in microwave ablation groups were significantly increased versus those in control group( P < 0. 05 or P < 0. 01),especially in the high dose group( P < 0. 05). Further,the percentages of CD4~+/CD8~+T cells in spleens of mice in high dose group was elevated versus those in moderate dose group and low dose group( P < 0. 05),as well as the control group( P < 0. 01). The percentages of CD8~+T cells were insignificant in each group( P > 0. 05). Conclusion: Microwave ablation can activate the immune functionality and inhibit the tumor growth in mice with colon cancer,and higher dose,more effective.
引文
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[14]Lonsdorf AS,Kuekrek H,Stern BV,et al.Intratumor Cp G-oligodeoxynucleotide injection induces protective antitumor T cell immunity[J].J Immunol,2003,171(8):3941-3946.
[2]郑灵巧,马彦明.大肠癌发病率不断攀升[J].老年健康,2011(5):4.
[3]Simoglou C,Gymnopoulou I,Babalis D,et al.Surgery of colon cancer in a district hospital[J].Hell J of Surg,2012,84(1):71-75.
[4]Whiteford MH,Whiteford HM,Yee LF,et al.Usefulness of FDGPET scan in the assessment of suspected metastatic or recurrent adenocarcinoma of the colon and rectum[J].Dis Colon Rectum,2000,43(6):759-767.
[5]Yue WW,Wang SR,Lu F,et al.Radiofrequency ablation vs.microwave ablation for patients with benign thyroid nodules:a propensity score matching study[J].Endocrine,2017,55(2):485-495.
[6]Korkusuz H,Happel C,Koch DA,et al.Combination of ultrasound-guided percutaneous microwave ablation and radioiodine therapy in benign thyroid disease:a 3-month follow-up study[J].Rofo,2016,188(1):60-68.
[7]Cornman-Homonoff J,Miller ZA,Smirniotopoulos J,et al.Preoperative percutaneous microwave ablation of long bone metastases using a parallel medullary approach for reduction of operative blood loss[J].J Vasc Interv Radiol,2017,28(7):1069-1071.
[8]Huang H,Hao S,Li F,et al.CD4+Th1 cell promote CD8+T cell survival,memory response,tumor localization and therapy by targeted delivery of interleukin 2 via acquired p MHCI complexes[J].Immunology,2007,120(2):148-159.
[9]Oizumi S,Strbo N,Pahwa S,et al.Molecular and cellular requirement for enhanced antigen cross-presentation to CD8 cytotoxic T lymphocytes[J].J Immunol,2007,179(4):2310-2317.
[10]Lardiere-Deguelte S,De Mestier L,Amroun KL,et al.Laparoscopic thermal ablation of splenic metastases initial experience and present aspects[J].J Visc Surg,2013,50(5):355-358.
[11]Liu QD,Song Y,Zhou NX,et al.Radiofrequency ablation of splenic tumors:a case series[J].J Gastrointestin Liver Dis,2013,22(1):105-108.
[12]Zerbini A,Pilli M,Penna A,et al.Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses[J].Cancer Res,2006,66(2):1139-1146.
[13]Pashenkov M,Go3ss G,Wagner C,et al.PhaseⅡtrial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma[J].J Clin Oncol,2006,24(36):5716-5724.
[14]Lonsdorf AS,Kuekrek H,Stern BV,et al.Intratumor Cp G-oligodeoxynucleotide injection induces protective antitumor T cell immunity[J].J Immunol,2003,171(8):3941-3946.