[关键词]
[摘要]
目的:制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞(autotumor specific cytotoxicity T lymphocytes,CTLs),观察其对乳腺癌患者骨髓微转移的治疗作用。方法:以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一科2007年3-12月间治疗的82例原发性乳腺癌(Ⅰ~Ⅲ期)术前患者(参加本实验的患者全部知情同意)骨髓微转移状况,将23例术前骨髓微转移阳性的乳腺癌患者随机分为2组:肿瘤特异性CTLs治疗组17例,IL2治疗对照组6例。术中取治疗组患者腋下淋巴结及外周血体外诱导培养肿瘤特异性CTLs,于术后10~14 d回输,观察特异性CTLs对乳腺癌骨髓微转移的治疗效果。结果:本组82例乳腺癌患者中23例(28.05%)骨髓微转移阳性,骨髓微转移的阳性率随临床分期、组织学分级的增加而增高,随 ER、PR 蛋白表达增强而降低。自乳腺癌患者外周血中成功分离、诱导培养出树突状细胞(dendritic cells,DCs),并经自体肿瘤抗原致敏,与患者腋窝淋巴结来源的淋巴细胞共培养后诱导产生自体肿瘤特异性CTLs。治疗组17例患者经特异性CTLs治疗后,14例转为阴性,转阴率为82.35%;对照组6例中仅1例转为阴性,转阴率为16.67%;肿瘤特异性CTLs的治疗效果显著高于对照治疗(P=000028)。结论:成功制备的肿瘤特异性CTLs对乳腺癌骨髓微转移有较好的治疗效果。
[Key word]
[Abstract]
Objective:To prepare autotumorspecific cytotoxicity T lymphocytes (CTLs) of breast cancer patients and to observe their therapeutic effects on bone marrow micrometastasis (BMM) of breast cancer. :Methods: :BMM in 82 patients with primary breast cancer (stage Ⅰto Ⅲ) , who were treated in the Fourth Affiliated Hospital of Hebei Medical University from March to December in 2007 (all the patients signed paper of informed consent), was exmined by flow cytometry using CK18 and CK19 as marker. Twentythree patients with BMM were randomly divided into two groups: 17 patients were treated with tumorspecific CTLs (therapy group), and 6 patients were treated with IL2 (control group). Tumorspecific CTLs were induced in vitro from axillary lymph nodes and peripheral blood of breast cancer patients in therapy group, and were reinfused into the same patient 1014 days after operation. The therapeutic effects of tumorspecific CTLs on BMM of breast cancer patients were observed. :Results: :Twentythree cases (28.05%) in 82 breast cancer patients were BMM positive as detected by FCM. BMM positive rates increased with the increase of clinical TNM stages and histological grades of breast cancer, and decreased with the increase of ER and PR protein expression in cancer tissues. Dendritic cells (DCs) were successfully isolated and induced from the peripheral blood of breast cancer patients. Tumorspecific CTLs were induced by coculturing lymphocytes from axillarey lymph nodes with autotumor antigenimpulsed DCs. Fourteen cases in the therapy group became negative of BMM after treatment with tumorspecific CTLs (14/19, 8235%). Only one case in the control group became negative of BMM after treatment with IL2 (1/6, 16.67%,〖HTSS〗:P=000028).: :Conclusion: :Tumorspecific CTLs have been successfully prepared and they show a satisfactory therapeutic effect on bone marrow micrometastasis of breast cancer.
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[基金项目]
河北省科技厅科技支撑课题资助项目(No.05276101D66;No.08276101D70);河北省高校强势特色学科基金资助项目