Enhancement of Anti-tumor Immune Response and Decrease of Recurrence Rate of Cervical Cancer by Low Dose Metronomic Chemotherapy of Cisplatin
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摘要: 目的 探讨低剂量顺铂周期化疗对机体抗肿瘤免疫应答及宫颈癌再发率的影响。方法 建立TC-1肿瘤细胞C57BL/6小鼠模型，分为3组（n=5）：对照组、低剂量组、高剂量组，绘制3组肿瘤生长曲线，用药结束后7 d检测3组小鼠外周血单核细胞（peripheral blood mononuclear cells，PBMCs）中HPV-E7特异性CD8+T细胞的数目。同法建立小鼠肿瘤模型、分组、治疗，治疗结束后7 d,切除肿瘤组织，下腹部对侧接种TC-1细胞，观察肿瘤再发率和小鼠生存率。结果 (1)顺铂低剂量周期疗法和高剂量疗法抗肿瘤作用相似。(2)低剂量周期疗法组PBMC中HPV-E7阳性的CD8+T数量显著高于高剂量组和对照组。(3)低剂量周期疗法组肿瘤再发率显著低于高剂量组和对照组；(4)低剂量周期疗法组肿瘤小鼠生存率显著高于高剂量组和对照组。结论 顺铂低剂量周期疗法能有效抑制肿瘤生长，其通过促进肿瘤特异性免疫应答，在一定程度上降低肿瘤再发，提高宿主生存率。Abstract: Objective To explore the effect of low dose metronomic chemotherapy of cisplatin on specifi c anti-tumor immune response and recurrence rate of cervical cancer. Methods Establish C57BL/6 mouse tumor model with TC-1 cells was established, the mice were divided into 3 groups (n=5) (control, low dose and high dose group). The tumor growth curve was drawn and the HPV-E7 specifi c CD8+ T cells number in PBMC were determined. The tumor model establishment, grouping and treatment were same as above, after 7 days treatment, the tumor was removed and the TC-1 cells were reinjected in the contralateral hypogastrium after 2 days of surgery. The tumor recurrence rate and survival rate were checked. Results (1)The antitumor effect was similar after low dose or high dose cisplatin treatment.(2) The HPV-E7 specifi c CD8+T cells in low dose group were significantly higher than that in control or high dose group.(3)The tumor recurrence rate in the low dose group was lower than that in control or high dose group.(4)The survival rate in low dose group was higher than that in control or high dose group. Conclusion Low dose metronomic chemotherapy of cisplatin can inhibit tumor growth effectively, through enhancing specific antitumor immune response, decrease the recurrence of tumor and increase the host survival rate in a certain extent.
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Key words:
- Cisplatin /
- Metronomic chemotherapy /
- Immune response /
- Cervical cancer /
- Dosage
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[1] Bellone S, El-Sahwi K, Cocco E, et al. Human papillomavirus type 16（HPV-16）virus-like particle L1-specifi c CD8+cytotoxic T lymphocytes（CTLs）are equally effective as E7-specific CD8+ CTLs in killing autologous HPV-16-positive tumor cells in cervical cancer patients:implications for L1 dendritic cell-based therapeutic vaccines[J].J Virol,2009,83(13):6779-89. [2] Gong L, Lou JY, Wang P, et al. Clinical evaluation of neoadjuvant chemotherapy followed by radical surgery in the management of stage IB2-IIB cervical cancer[J]. Int J Gynaecol Obstet, 2012， 11 7(1):23-6. [3] Daenen LG,Shaked Y,Man S, et al. Low-dose metronomic cyclophosphamide combined with vascular disrupting therapy induces potent antitumor activity in preclinical human tumor xenograft models[J]. Mol Cancer Ther,2009,8(10):2872-81. [4] Naito S,von Eschenbach AC,Giavazzi R, et al. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice[J]. Cancer Res,1986,46(8):4109-15. [5] Broomfield S,Currie A,van der Most RG,et al. Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy[J]. Cancer Res,2005,65 (17):7580-4. [6] Chen CA,Ho CM,Chang MC, et al. Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory t lymphocytes and inhibiting tumor angiogenesis[J]. Mol Ther,2010,18(6): 1233-43. [7] Zhong H, Han B, Tourkova IL, et al. Low-dose paclitaxel prior to intratumoral dendritic cell vaccine modulates intratumoral cytokine network and lung cancer growth[J]. Clin Cancer Res,2007,13(18 Pt 1): 5455-62. [8] Hermans IF, Chong TW, Palmowski MJ, et al. Synergistic effect of metronomic dosing of cyclophosphamide combined with specifi c antitumor immunotherapy in a murine melanoma model [J]. Cancer Res,2003,63(23):8408-13.
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