DC-CIK免疫细胞治疗晚期乳腺癌患者的临床疗效
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摘要
目的:观察自体DC联合CIK细胞治疗晚期乳腺癌患者的安全性及临床疗效,并分析相关预后因素。方法:回顾性分析2011年8月至2014年12月在解放军第81医院进行DC-CIK细胞治疗的42例晚期乳腺癌患者临床资料,采用实体瘤疗效评价标准评价近期疗效,并观察DC-CIK细胞治疗的安全性。分析患者生存期,评价远期疗效,单因素及多因素分析预后因素,并采用配对t检验分析患者治疗前后免疫功能。结果:42例晚期乳腺癌患者经DC-CIK细胞治疗后,客观缓解率为38.1%(16/42),疾病控制率为61.9%(26/42);1年生存率为59%,2年生存率为48%,3年生存率为48%;肿瘤标记物CA153治疗后显著性降低;外周血淋巴细胞亚群除辅助性T细胞(CD3~+CD4~+)水平显著性升高外,其他淋巴细胞亚群无显著性变化。单因素分析结果显示,肿瘤部位(P=0.012)、治疗前CA153水平(P=0.000)是DC-CIK细胞治疗预后的影响因素;多因素分析结果显示,治疗前CA153水平(P=0.003)是DC-CIK细胞治疗的独立预后因素。结论:晚期乳腺癌患者经DC-CIK细胞治疗后,无明显不良反应,可能提高患者长期生存率,产生临床获益,安全可行。
Objective: To evaluate the clinical efficacy and safety of dendritic cells( DCs) combined with cytokine-induced killer( CIK) cells in the treatment of advanced breast cancer,and to investigate the relevant prognostic factors.Methods: The clinical documents of 42 patients with advanced breast cancer that received DC / CIK treatment in 81 st Hospital of PLA from August 2011 to December 2014 were retrospectively analyzed. Short-term curative effect was evaluated by Response Evaluation Criteria in Solid Tumors( RECIST) and the safety of DC-CIK therapy was observed. Overall survival of 42 patients was analyzed to evaluate the long-term curative effect. Univariate and multivariate analyses were used to analyze prognostic factors. The immunologic function was evaluated by paired T-test. Results: After the DC-CIK therapy,the overall response rate was 38. 1%( 16 /42),the disease control rate was 61. 9%( 26 /42),and the one-year,twoyear and three-year survival rates were 59%,48% and 48%,respectively. CA153 was significantly decreased after the treatment. In addition to a significant increase in the CD4~+ level,the other peripheral blood lymphocyte subsets didn't change significantly. Univariate analysis showed that the onset area( P = 0. 012) and the CA153 value before treatment( P = 0. 000) were the influence factors for the prognosis of cell immune therapy. Multivariate analysis showed that the CA153 value before treatment was an independent influence factor for the prognosis of cell immune therapy. Conclusion:The DC-CIK therapy is a safe and feasible therapeutic approach. It may improve the long-term survival rate of patients with advanced breast cancer.
Objective: To evaluate the clinical efficacy and safety of dendritic cells( DCs) combined with cytokine-induced killer( CIK) cells in the treatment of advanced breast cancer,and to investigate the relevant prognostic factors.Methods: The clinical documents of 42 patients with advanced breast cancer that received DC / CIK treatment in 81 st Hospital of PLA from August 2011 to December 2014 were retrospectively analyzed. Short-term curative effect was evaluated by Response Evaluation Criteria in Solid Tumors( RECIST) and the safety of DC-CIK therapy was observed. Overall survival of 42 patients was analyzed to evaluate the long-term curative effect. Univariate and multivariate analyses were used to analyze prognostic factors. The immunologic function was evaluated by paired T-test. Results: After the DC-CIK therapy,the overall response rate was 38. 1%( 16 /42),the disease control rate was 61. 9%( 26 /42),and the one-year,twoyear and three-year survival rates were 59%,48% and 48%,respectively. CA153 was significantly decreased after the treatment. In addition to a significant increase in the CD4~+ level,the other peripheral blood lymphocyte subsets didn't change significantly. Univariate analysis showed that the onset area( P = 0. 012) and the CA153 value before treatment( P = 0. 000) were the influence factors for the prognosis of cell immune therapy. Multivariate analysis showed that the CA153 value before treatment was an independent influence factor for the prognosis of cell immune therapy. Conclusion:The DC-CIK therapy is a safe and feasible therapeutic approach. It may improve the long-term survival rate of patients with advanced breast cancer.
引文
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[12]田晓刚.乳腺癌术后放疗患者T淋巴细胞亚群与ER、PR、Her-2表达的相关性研究[J].中国癌症防治杂志,2012,4(4):315-318.DOI:10.3969/j.issn.1674-5671.2012.04.04.
[13]赵树艳.淋巴细胞亚群自然杀伤细胞糖类抗原153细胞角蛋白19和癌胚抗原在乳腺癌诊断中的应用价值[J].中国肿瘤临床与康复,2015,22(3):279-282.
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[15]张佳楠,吴昌平,蒋敬庭.三阴乳腺癌的免疫治疗研究进展[J].中国医药生物技术,2015,10(4):306-308.DOI:10.3969/cmba.j.issn.1673-713X.2015.04.005.
[16]刘卫国.免疫治疗对乳腺癌患者术后免疫功能和生存状况的影响[J].中国现代普通外科进展,2015,18(3):189-192.DOI:10.3969/j.issn.1009-9905.2015.03.006.
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[18]韩策,尤向辉,聂娜,等.肿瘤免疫治疗研究进展[J].陕西医学杂志,2015,36(4):502-503.DOI:10.3969/j.issn.1000-7377.2015.04.055.
[19]HELMS M W,PRESCHER J A,CAO Y A,et al.IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy[J].Cancer Immunol Immunother,2010,59(9):1325-1334.DOI:10.1007/s00262-010-0860-y.
[20]WANG Q J,WANG H,PAN K,et al.Comparative study on antitumor immune response of autologous cytokine induced killer cells dendritic cells-CIK(DC-CIK)and semi-allogeneic DC-CIK[J].Chin J Cancer,2010,29(7):641-647.DOI:10.5732/cjc.009.10772.
[21]NELSON H D,ZAKHCR B,CANTOR A,et al.Risk factors for breast cancer for women aged 40 to 49 years:a systematic review and meta-analysis[J].Ann Intern Med,2012,156(9):635-648.DOI:10.7326/0003-4819-156-9-201205010-00006.
[22]王征,翟晓健,叶新平,等.三阴性乳腺癌应用CIK细胞联合化疗治疗观察[J].中国医学工程,2013(11):20-21.
[23]朱欢欢,马东初,丁震宇,等.DC-CIK治疗对辅助化疗后三阴乳腺癌的临床疗效观察[J].解放军医药杂志,2015,27(1):48-51.DOI:10.3969/j.issn.2095-140X.2015.01.009.
[24]张佳楠,吴昌平,蒋敬庭.三阴乳腺癌的免疫治疗研究进展[J].中国医药生物技术,2015,10(4):306-308.DOI:10.3969/cmba.j.issn.1673-713X.2015.04.005.
[25]MAYER I A,ABRAMSON V G,LEHMANN B D,et al.New stragegies for triple-negative breast cancer-deciphering the heterogeneity[J].Clin Cancer Res,2014,20(4):782-790.DOI:10.1158/1078-0432.CCR-13-0583.
[26]BUDD G T,BARLOW W E,MOORE H C,et al.SWOG S0221:a phaseⅢtrial comparing chemotherapy schedules in high-risk early-stage breast cancer[J].J Clin Oncol,2015,33(1):58-64.DOI:10.1200/JCO.2014.56.3296.
[27]CUZICK J,SESTAK I,BAUM M,et al.Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer:10-year analysis of the ATAC trial[J].Lancet Oncol,2010,11(12):1135-1141.DOI:10.1016/S1470-2045(10)70257-6.
[28]DECENSI A,COSTA A.Recent advances in cancer chemoprevention,with emphasis on breast and colorectal cancer[J].Eur J Cancer,2000,36(6):694-709.DOI:10.1016/S0959-8049(00)00040-X.
[29]WANG Z X,CAO J X,WANG M,et al.Adoptive cellular immunotherapy for the treatment of patients with breast cancer:a metaanalysis[J].Cytotherapy,2014,16(7):934-945.DOI:10.1016/j.jcyt.2014.02.011.
[30]TABARIES S,OUELLET V,HSU B E,et al.Granulocytic immune infiltrates are essential for the efficient formation of breast cancer liver metastases[J].Breast Cancer Res,2015,17(1):1-18.DOI:10.1186/s13058-015-0558-3.
[2]冀为,周岩,牛瑞芳.外周血T淋巴细胞亚群与不同分子分型乳腺癌患者无病生存的相关性研究[J].中国肿瘤临床,2014,41(21):1363-1367.DOI:10.3969/j.issn.1000-8179.20141221.
[3]江泽飞.2014年圣安东尼奥国际乳腺癌会议热点问题解读[J].中华医学杂志,2015,95(12):891-893.DOI:10.3760/cma.j.issn.0376-2491.2015.12.004.
[4]陈锦飞,顾冬英.2015 St.Gallen及ASCO会议乳腺癌治疗进展[J].中国肿瘤外科杂志,2015,7(3):150-153.DOI:10.3969/j.issn.1674-4136.2015.03.004.
[5]倪志强,方艳秋,刘多,等.DC-CIK联合化疗对乳腺癌患者免疫功能、无进展生存期及生活质量的影响[J].中国妇幼保健,2013,28(31):5134-5137.DOI:10.7620/zgfybj.j.issn.1001-4411.2013.28.13.
[6]邵彬,张洁.自体外周血造血干细胞支持下高剂量化疗对晚期乳腺癌患者的生活质量研究[J].肿瘤防治研究,2015,42(2):145-149.DOI:10.3971/j.issn.1000-8578.2015.02.010.
[7]底玮,沈方臻.DC-CIK细胞与顺铂对乳腺癌细胞杀伤作用的研究[J].中外医疗,2015,8:124-126.DOI:10.3969/j.issn.1674-0742.2015.08.058.
[8]CUI Y,YANG X,ZHU W,et al.Immune response,clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients[J].Oncol Lett,2013,6(2):537-541.DOI:10.3892/ol.2013.1376.
[9]YANG L,REN B,LI H,et al.Enhanced antitumor effects of DCactivated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients[J].Cancer Immunol Immunother,2013,62(1):65-73.DOI:10.1007/s00262-012-1311-8.
[10]ROSENBERG S A,RESTIFO N P,YANG J C,et al.Adoptive cell transfer:a clinical path to effective cancer immunotherapy[J].Nat Rev Cancer,2008,8(4):299-308.DOI:10.1038/nrc2355.
[11]张铁英,康丽花,刘远航,等.不同分子亚型乳腺癌T淋巴细胞和NK细胞检测的临床意义[J].中国妇幼保健,2015,30(21):3594-3595.DOI:10.7620/zgfybj.j.issn.1001-4411.2015.21.23.
[12]田晓刚.乳腺癌术后放疗患者T淋巴细胞亚群与ER、PR、Her-2表达的相关性研究[J].中国癌症防治杂志,2012,4(4):315-318.DOI:10.3969/j.issn.1674-5671.2012.04.04.
[13]赵树艳.淋巴细胞亚群自然杀伤细胞糖类抗原153细胞角蛋白19和癌胚抗原在乳腺癌诊断中的应用价值[J].中国肿瘤临床与康复,2015,22(3):279-282.
[14]EISENHAUER E A,THERASSE P,BOGAERTS J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J].Eur J Cancer,2009,45(13):228-247.DOI:10.1016/j.ejca.2008.10.026.
[15]张佳楠,吴昌平,蒋敬庭.三阴乳腺癌的免疫治疗研究进展[J].中国医药生物技术,2015,10(4):306-308.DOI:10.3969/cmba.j.issn.1673-713X.2015.04.005.
[16]刘卫国.免疫治疗对乳腺癌患者术后免疫功能和生存状况的影响[J].中国现代普通外科进展,2015,18(3):189-192.DOI:10.3969/j.issn.1009-9905.2015.03.006.
[17]NEUMAN H B,WEISS J M,SCHRAG D,et al.Patient demographic and tumor characteristics influencing on cologist follow-up frequency in older breast cancer survivors[J].Ann Surg Oncol,2013,20(13):4128-4136.DOI:10.1245/s10434-013-3170-8.
[18]韩策,尤向辉,聂娜,等.肿瘤免疫治疗研究进展[J].陕西医学杂志,2015,36(4):502-503.DOI:10.3969/j.issn.1000-7377.2015.04.055.
[19]HELMS M W,PRESCHER J A,CAO Y A,et al.IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy[J].Cancer Immunol Immunother,2010,59(9):1325-1334.DOI:10.1007/s00262-010-0860-y.
[20]WANG Q J,WANG H,PAN K,et al.Comparative study on antitumor immune response of autologous cytokine induced killer cells dendritic cells-CIK(DC-CIK)and semi-allogeneic DC-CIK[J].Chin J Cancer,2010,29(7):641-647.DOI:10.5732/cjc.009.10772.
[21]NELSON H D,ZAKHCR B,CANTOR A,et al.Risk factors for breast cancer for women aged 40 to 49 years:a systematic review and meta-analysis[J].Ann Intern Med,2012,156(9):635-648.DOI:10.7326/0003-4819-156-9-201205010-00006.
[22]王征,翟晓健,叶新平,等.三阴性乳腺癌应用CIK细胞联合化疗治疗观察[J].中国医学工程,2013(11):20-21.
[23]朱欢欢,马东初,丁震宇,等.DC-CIK治疗对辅助化疗后三阴乳腺癌的临床疗效观察[J].解放军医药杂志,2015,27(1):48-51.DOI:10.3969/j.issn.2095-140X.2015.01.009.
[24]张佳楠,吴昌平,蒋敬庭.三阴乳腺癌的免疫治疗研究进展[J].中国医药生物技术,2015,10(4):306-308.DOI:10.3969/cmba.j.issn.1673-713X.2015.04.005.
[25]MAYER I A,ABRAMSON V G,LEHMANN B D,et al.New stragegies for triple-negative breast cancer-deciphering the heterogeneity[J].Clin Cancer Res,2014,20(4):782-790.DOI:10.1158/1078-0432.CCR-13-0583.
[26]BUDD G T,BARLOW W E,MOORE H C,et al.SWOG S0221:a phaseⅢtrial comparing chemotherapy schedules in high-risk early-stage breast cancer[J].J Clin Oncol,2015,33(1):58-64.DOI:10.1200/JCO.2014.56.3296.
[27]CUZICK J,SESTAK I,BAUM M,et al.Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer:10-year analysis of the ATAC trial[J].Lancet Oncol,2010,11(12):1135-1141.DOI:10.1016/S1470-2045(10)70257-6.
[28]DECENSI A,COSTA A.Recent advances in cancer chemoprevention,with emphasis on breast and colorectal cancer[J].Eur J Cancer,2000,36(6):694-709.DOI:10.1016/S0959-8049(00)00040-X.
[29]WANG Z X,CAO J X,WANG M,et al.Adoptive cellular immunotherapy for the treatment of patients with breast cancer:a metaanalysis[J].Cytotherapy,2014,16(7):934-945.DOI:10.1016/j.jcyt.2014.02.011.
[30]TABARIES S,OUELLET V,HSU B E,et al.Granulocytic immune infiltrates are essential for the efficient formation of breast cancer liver metastases[J].Breast Cancer Res,2015,17(1):1-18.DOI:10.1186/s13058-015-0558-3.