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局部和局部进展性肾细胞癌患者术后肿瘤裂解物脉冲树突状细胞和细胞因子诱导的杀伤细胞免疫治疗的随机对照试验。

A randomized controlled trial of postoperative tumor lysate-pulsed dendritic cells and cytokine-induced killer cells immunotherapy in patients with localized and locally advanced renal cell carcinoma.

机构信息

Department of Urology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.

出版信息

Chin Med J (Engl). 2012 Nov;125(21):3771-7.

PMID:23106871
Abstract

BACKGROUND

It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma (RCC) after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate (TL)-pulsed dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with localized or locally advanced RCC.

METHODS

From January 2001 to July 2009, we collected 137 patients that met the selection criteria and randomly divided them into three groups. After surgery, immunotherapy with TL-pulsed DCs-CIK cells (DC-CIK group) and interferon (IFN)-α (IFN-α group) was performed in 46 patients, respectively. The other 45 patients received no postoperative adjuvant therapy (the control group). The changes in the numbers of T lymphocyte subsets, including CD4(+)CD25(high) regulatory T cells (Treg), were determined before the operation and after immunotherapy. The overall survival was compared among the three groups.

RESULTS

An increase of the CD4(+)/CD8(+) ratio and a decrease of CD4(+)CD25(high) cells were observed after TL-pulsed DC-CIK cells or IFN-a immunotherapy. All patients tolerated the TL-pulsed DC-CIK cells immunotherapy very well, and side effects in the DC-CIK group were less than in the IFN-α group. The metastasis and recurrence rates were significantly decreased after TL-pulsed DC-CIK cells or IFN-α immunotherapy compared with the control group (P < 0.01). The Log-rank test showed that the overall survival rates were significantly higher in the DC-CIK group and IFN-α group than that in the control group (P < 0.01), but there was no difference between the DC-CIK group and IFN-α group (P > 0.05).

CONCLUSION

Postoperative immunotherapy with TL-pulsed DC-CIK cells may prevent recurrence/metastasis and increase the overall survival rate after surgery in localized or locally advanced RCC.

摘要

背景

抑制局部或局部晚期肾细胞癌(RCC)手术后的局部复发或远处转移仍然是一个挑战。我们研究了使用自体肿瘤裂解物(TL)脉冲树突状细胞(DC)和细胞因子诱导的杀伤(CIK)细胞进行免疫治疗在局部或局部晚期 RCC 患者中的可行性、安全性和疗效。

方法

从 2001 年 1 月至 2009 年 7 月,我们收集了符合选择标准的 137 名患者,并将其随机分为三组。手术后,分别对 46 例患者进行 TL 脉冲 DC-CIK 细胞(DC-CIK 组)和干扰素(IFN)-α(IFN-α 组)免疫治疗。另外 45 例患者未接受术后辅助治疗(对照组)。在手术前和免疫治疗后,检测 T 淋巴细胞亚群(包括 CD4+CD25(高)调节性 T 细胞(Treg))的数量变化。比较三组患者的总生存率。

结果

TL 脉冲 DC-CIK 细胞或 IFN-α 免疫治疗后,CD4+/CD8+比值增加,CD4+CD25(高)细胞减少。所有患者均能很好地耐受 TL 脉冲 DC-CIK 细胞免疫治疗,且 DC-CIK 组的副作用少于 IFN-α 组。TL 脉冲 DC-CIK 细胞或 IFN-α 免疫治疗后,转移和复发率明显低于对照组(P < 0.01)。Log-rank 检验显示,DC-CIK 组和 IFN-α 组的总生存率明显高于对照组(P < 0.01),但 DC-CIK 组与 IFN-α 组之间无差异(P > 0.05)。

结论

局部或局部晚期 RCC 手术后免疫治疗 TL 脉冲 DC-CIK 细胞可能预防复发/转移,并提高术后总生存率。

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