CIK联合DC细胞免疫治疗在转移性乳腺癌中的临床应用
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摘要
目的：通过比较对照组（单纯化疗组）与联合治疗组（DC-CIK细胞免疫治疗联合化疗组）的疗效及毒副作用，客观地评价DC-CIK细胞免疫疗法治疗转移性乳腺癌的临床疗效，为转移性乳腺癌的个体化综合治疗模式提供新的思路，获得更好的临床疗效。
方法：本研究对41例转移性乳腺癌患者进行研究，所有患者均已行手术治疗及术后辅助化疗，有明确的组织病理学检查，均由B超、CT、MRI及骨扫描确诊证实为转移性乳腺癌的女性患者。入选患者被随机分为单纯化疗组，即应用多西他赛联合表阿霉素（TA）方案化疗，与联合治疗组（DC-CIK细胞免疫治疗联合TA方案治疗），联合治疗组采用常规化疗与DC-CIK细胞免疫治疗间隔进行的方法。对两组的治疗有效率（RR）、疾病控制率（DCR）、毒副反应、治疗前后T淋巴细胞亚群的变化及生活质量进行比较。疗效评价按照近年普遍应用的实体瘤疗效评价标准(RECIST)评价疗效。化疗反应按照WHO标准分为0~Ⅳ度，利用SPSS13.0软件包进行数据处理。
结果：（1）单纯化疗组经过TA方案化疗后，RR为60.0%，DCR为75.0%。（2）DC-CIK细胞免疫治疗联合化疗组经过治疗后，RR为71.4%，DCR为85.7%。联合治疗组RR及DCR有所提高，但无统计学差异，（p＞0.05）。（3）单纯化疗组的毒副反应主要表现为脱发及白细胞减少，发生率分别为80.0%及85.0%，联合治疗组的主要毒副反应同样表现为脱发及白细胞减少，发生率分别为76.2%及71.4%，两组之间差异无统计学意义，（p＞0.05）。经过DC-CIK细胞免疫治疗后有2例患者出现一过性发热，未观察到明显的不良反应。（4）联合治疗组患者经过DC-CIK细胞免疫治疗后，T淋巴细胞亚群发生变化，CD3~+、CD3~+/CD4~+、CD3~+/CD8~+、CD4~+/CD8~+、CD3-/CD16~+56~+上升，CD3~+/CD8~+明显下降，机体免疫力提升，治疗前后相比差异有统计学意义，（p＜0.05）。（5）联合治疗组患者经过DC-CIK细胞免疫治疗后，在疲倦乏力、食欲不振、失眠盗汗方面明显缓解，与单纯化疗组相比，差异有统计学差异，（p＜0.05）。
结论：与单纯化疗组相比，DC-CIK细胞免疫治疗联合化疗组有效率（RR）和疾病控制率（DCR）有所提高，近期疗效较好，除一过性发热外，未观察到明显毒副反应。同时联合治疗组患者经过DC-CIK免疫治疗后，T淋巴细胞亚群发生变化，免疫抑制状态得到改善，机体免疫力提升，生活质量显著提高，DC-CIK细胞免疫治疗在转移性乳腺癌中有较好的疗效。
Objective: To observe the efficacy and toxicity of the combination ofchemotherapy with DC-CIK cellular immunotherapy and chemotherapy alonein metastatic breast cancer (MBC) patients, provide a new method for totalmanagement of MBC patients，and obtain a better clinical efficacy.
Methods: This study was executed on41patients, all the patients wereafter the operation and the postoperative adjuvant chemotherapy, with thespecific histopathological examination, and proved to be MBC throughultrasonic B，CT，MRI or bone scan. All the patients were randomly separatedinto two groups, chemotherapy group (TA regimen) and combination treatmentgroup (DC-CIK cellular immunotherapy combined with TA regimen). Theresponse rate (RR), disease control rate (DCR), adverse reactions of thechemotherapy and DC-CIK cellular immunotherapy, the variance ofT-Lymphocyte Subsets before and after the treatment, and the quality of lifewere observed in the both groups. The therapeutic evaluation were evaluatedfollowing the RECIST (Response Evaluation Criteria In Solid Tumors), whichis used generally in these years. The chemotherapy adverse reactions weredivided into0～Ⅳ grades according to the WHO criterion. And the datas wereprocessed by the software of SPSS13.0.
Results:（1）Among the patients in chemotherapy group, about60.0%patients achieved to RR after the TA chemotherapy, and about75.0%patientsachieved to DCR.(2) Among the patients in combination treatment group,about71.0%patients achieved to RR after the treatment, and about85.7%patients achieved to DCR. Both the RR and the DCR were increased in thecombination treatment group，but this result has no significantly statistical differences（p＞0.05）.(3) The main adverse reactions of the chemotherapygroup were performed as alopecia and leukocytopenia, the occurring rates were80.0%and85.0%respectively. And the main adverse reactions of thecombination group performed the same as the other group, but the occurringrates were76.2%and71.4%， this result has no significantly statisticaldifferences（p＞0.05）. After the DC-CIK cellular immunotherapy, about twopatients in the combination group got a transient fever, and were didn'tdiscover other severe adverse reactions in this group.(4) After the DC-CIKcellular immunotherapy, the T-Lymphocyte Subsets of the patients in thecombination treatment group changed. The results of the CD3~+、CD3~+/CD4~+、CD3~+/CD8~+、CD4~+/CD8~+、CD3-/CD16~+56~+were increased, and CD3~+/CD8~+decreased obviously. And the body immunity was improved，this result hassignificantly statistical differences （p＜0.05）.(5) The patients in thecombination treatment group felt much better in tired fatigue, anepithymia，andsleepless night sweats after the DC-CIK cellular immunotherapy, in comparingof the chemotherapy group. And this result has significantly statisticaldifferences，（p＜0.05）.
Conclusions: In comparing of the chemotherapy group, the RR and DCRof the combination treatment group was increased, and the recently curativeeffect was good. Except the transient fever, we didn't discover other obviousadverse reactions in the combination group. In the combination group, patientswho were after the DC-CIK cellular immunotherapy got the T-Cell Subsetschanged, the immunosuppressive states ameliorated, the body immunityimproved, the quality of life enhanced obviously. All the above clarified thatthe combination of DC-CIK cellular immunotherapy and TA planchemotherapy has a promising prospect in treating metastatic breast cancer.
方法：本研究对41例转移性乳腺癌患者进行研究，所有患者均已行手术治疗及术后辅助化疗，有明确的组织病理学检查，均由B超、CT、MRI及骨扫描确诊证实为转移性乳腺癌的女性患者。入选患者被随机分为单纯化疗组，即应用多西他赛联合表阿霉素（TA）方案化疗，与联合治疗组（DC-CIK细胞免疫治疗联合TA方案治疗），联合治疗组采用常规化疗与DC-CIK细胞免疫治疗间隔进行的方法。对两组的治疗有效率（RR）、疾病控制率（DCR）、毒副反应、治疗前后T淋巴细胞亚群的变化及生活质量进行比较。疗效评价按照近年普遍应用的实体瘤疗效评价标准(RECIST)评价疗效。化疗反应按照WHO标准分为0~Ⅳ度，利用SPSS13.0软件包进行数据处理。
结果：（1）单纯化疗组经过TA方案化疗后，RR为60.0%，DCR为75.0%。（2）DC-CIK细胞免疫治疗联合化疗组经过治疗后，RR为71.4%，DCR为85.7%。联合治疗组RR及DCR有所提高，但无统计学差异，（p＞0.05）。（3）单纯化疗组的毒副反应主要表现为脱发及白细胞减少，发生率分别为80.0%及85.0%，联合治疗组的主要毒副反应同样表现为脱发及白细胞减少，发生率分别为76.2%及71.4%，两组之间差异无统计学意义，（p＞0.05）。经过DC-CIK细胞免疫治疗后有2例患者出现一过性发热，未观察到明显的不良反应。（4）联合治疗组患者经过DC-CIK细胞免疫治疗后，T淋巴细胞亚群发生变化，CD3~+、CD3~+/CD4~+、CD3~+/CD8~+、CD4~+/CD8~+、CD3-/CD16~+56~+上升，CD3~+/CD8~+明显下降，机体免疫力提升，治疗前后相比差异有统计学意义，（p＜0.05）。（5）联合治疗组患者经过DC-CIK细胞免疫治疗后，在疲倦乏力、食欲不振、失眠盗汗方面明显缓解，与单纯化疗组相比，差异有统计学差异，（p＜0.05）。
结论：与单纯化疗组相比，DC-CIK细胞免疫治疗联合化疗组有效率（RR）和疾病控制率（DCR）有所提高，近期疗效较好，除一过性发热外，未观察到明显毒副反应。同时联合治疗组患者经过DC-CIK免疫治疗后，T淋巴细胞亚群发生变化，免疫抑制状态得到改善，机体免疫力提升，生活质量显著提高，DC-CIK细胞免疫治疗在转移性乳腺癌中有较好的疗效。
Objective: To observe the efficacy and toxicity of the combination ofchemotherapy with DC-CIK cellular immunotherapy and chemotherapy alonein metastatic breast cancer (MBC) patients, provide a new method for totalmanagement of MBC patients，and obtain a better clinical efficacy.
Methods: This study was executed on41patients, all the patients wereafter the operation and the postoperative adjuvant chemotherapy, with thespecific histopathological examination, and proved to be MBC throughultrasonic B，CT，MRI or bone scan. All the patients were randomly separatedinto two groups, chemotherapy group (TA regimen) and combination treatmentgroup (DC-CIK cellular immunotherapy combined with TA regimen). Theresponse rate (RR), disease control rate (DCR), adverse reactions of thechemotherapy and DC-CIK cellular immunotherapy, the variance ofT-Lymphocyte Subsets before and after the treatment, and the quality of lifewere observed in the both groups. The therapeutic evaluation were evaluatedfollowing the RECIST (Response Evaluation Criteria In Solid Tumors), whichis used generally in these years. The chemotherapy adverse reactions weredivided into0～Ⅳ grades according to the WHO criterion. And the datas wereprocessed by the software of SPSS13.0.
Results:（1）Among the patients in chemotherapy group, about60.0%patients achieved to RR after the TA chemotherapy, and about75.0%patientsachieved to DCR.(2) Among the patients in combination treatment group,about71.0%patients achieved to RR after the treatment, and about85.7%patients achieved to DCR. Both the RR and the DCR were increased in thecombination treatment group，but this result has no significantly statistical differences（p＞0.05）.(3) The main adverse reactions of the chemotherapygroup were performed as alopecia and leukocytopenia, the occurring rates were80.0%and85.0%respectively. And the main adverse reactions of thecombination group performed the same as the other group, but the occurringrates were76.2%and71.4%， this result has no significantly statisticaldifferences（p＞0.05）. After the DC-CIK cellular immunotherapy, about twopatients in the combination group got a transient fever, and were didn'tdiscover other severe adverse reactions in this group.(4) After the DC-CIKcellular immunotherapy, the T-Lymphocyte Subsets of the patients in thecombination treatment group changed. The results of the CD3~+、CD3~+/CD4~+、CD3~+/CD8~+、CD4~+/CD8~+、CD3-/CD16~+56~+were increased, and CD3~+/CD8~+decreased obviously. And the body immunity was improved，this result hassignificantly statistical differences （p＜0.05）.(5) The patients in thecombination treatment group felt much better in tired fatigue, anepithymia，andsleepless night sweats after the DC-CIK cellular immunotherapy, in comparingof the chemotherapy group. And this result has significantly statisticaldifferences，（p＜0.05）.
Conclusions: In comparing of the chemotherapy group, the RR and DCRof the combination treatment group was increased, and the recently curativeeffect was good. Except the transient fever, we didn't discover other obviousadverse reactions in the combination group. In the combination group, patientswho were after the DC-CIK cellular immunotherapy got the T-Cell Subsetschanged, the immunosuppressive states ameliorated, the body immunityimproved, the quality of life enhanced obviously. All the above clarified thatthe combination of DC-CIK cellular immunotherapy and TA planchemotherapy has a promising prospect in treating metastatic breast cancer.
引文
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