目的： 研究多肽负载树突状细胞（dendritic cell，DC）联合细胞因子诱导的杀伤细胞（cytokine-induced killer cell，CIK）对激素难治性前列腺癌（hormone refractory metastatic prostate cancer，HRPC）患者免疫治疗的效果。 方法： 选择无锡市第四人民医院中西医结合科收治的HLA-A2+ HRPC患者26例，分离外周血单个核细胞，其中贴壁细胞经GM-CSF、IL-4联合诱导培养为成熟DC，负载前列腺癌特异性抗原（prostate specific antigen，PSA）、前列腺酸性磷酸酶（prostatic acid phosphatase，PAP）、前列腺特异性膜抗原（prostate specific membrane antigen，PSMA）三个多肽，制备成DC疫苗，经患者腹股沟皮内注射；未贴壁细胞经IFN-γ、IL-2、抗CD3单抗、IL-1体外诱导培养成CIK，经静脉回输给患者。在治疗后1周进行迟发型超敏反应（delayed type hypersensitivity，DTH）检测，在患者治疗前后进行血清中细胞因子和PSA检测，治疗结束后4周进行短期疗效评价。 结果： 26例HRPC患者对DC联合CIK治疗的耐受良好。治疗后患者血清中IL-2、IL-12、IFN-γ水平较治疗前显著升高（上升幅度分别为65.07%、67.69%和125.38%，P<0.05 或P<0.01），TNF-α和IL-10水平变化不大；DTH 的阳性率为435%（10/23）；7例患者的CD8+IFN-γ+T细胞比例较治疗前显著提高\[（8.95±2.74）% vs （0.39±0.15）%，P<0.01\]；8/26例患者的PSA下降，降幅为13%~66%。26例患者短期疗效评价，3例PR、4例PD、19例SD，所有患者治疗中未出现明显不良反应。 结论： 多肽负载DC联合CIK治疗HRPC能激发患者的免疫应答、诱导Th1型细胞因子的分泌，近期疗效良好，是一种安全的治疗方法。

Objective:To investigate the efficacy of polypeptide-loaded dendritic cells (DCs) in combination with cytokine-induced killer cells (CIKs) against hormone refractory metastatic prostate cancer (HRPC) patients. Methods: Twenty-six HLA-A2+ patients with HRPC were enrolled from the Department of Chinese Traditional and Western Medicine of the Wuxi No.4 People’s Hospital. Peripheral blood mononuclear cells (PBMCs) were separated, and the adherent cells were induced into DCs by GM-CSF and IL-4. Then DCs were loaded with three peptides (prostate specific antigen, PSA; prostatic acid phosphatase, PAP; prostate specific membrane antigen, PSMA) to prepare DC vaccine and were injected intracutaneously. The un-adherent cells of PBMCs were induced into CIK by IFN-γ, IL-2, CD3 monoclonal antibody and IL-1, and were injected intravenously. Delayed type hypersensitivity (DTH) was detected one week after treatment, and cytokine and PSA in serum were determined before and after treatment. The short-term efficacy was evaluated 4 weeks after treatment. Results: DC-CIK therapy was well tolerated in 26 HRPC patients. The serum IL-2, IL-12, and IFN-γ levels after therapy were significantly increased (increased 65.07%, 67.69% and 12538%, P<0.05 or P<001), while TNF-α and IL-10 levels were unchanged. The positive rate of DTH was 43.5% (10/23). The proportion of CD8+IFNγ+ cells after therapy was significantly increased (\[8.95±2.74\]% vs \[0.39±015\]%, P<0.01). A decrease of PSA (13% to 66%) was observed in 8 of 26 patients. The short-term efficacy of 26 HRPC patients was evaluated, with 3 PR, 4 PD, and 19 SD after treatment, and no severe adverse reaction was observed. Conclusion: The polypeptide-loaded DC in combination with CIK therapy can elicit specific immune responses in HRPC patients, and induce type I cytokine secretion with well short-term clinical efficacy, indicating that DC-CIK therapy is a safe treatment for HRPC.

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