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原发性手术效果欠佳会导致卵巢癌患者出现不良免疫变化。

Sub-optimal primary surgery leads to unfavorable immunological changes in ovarian cancer patients.

作者信息

Nowak Marek, Głowacka Ewa, Lewkowicz Przemysław, Banasik Małgorzata, Szyłło Krzysztof, Zimna Kinga, Bednarska Katarzyna, Klink Magdalena

机构信息

Department of Operative Gynecology and Gynecologic Oncology, Polish Mother's Memorial Hospital - Research Institute, 281/289 Rzgowska Str., 93-338, Lodz, Poland.

Laboratory Diagnostics Centre, Polish Mother's Memorial Hospital - Research Institute, 281/289 Rzgowska Str., 93-338, Lodz, Poland.

出版信息

Immunobiology. 2018 Jan;223(1):1-7. doi: 10.1016/j.imbio.2017.10.021. Epub 2017 Oct 5.

Abstract

Primary cytoreduction, followed by chemotherapy, is a standard treatment of patients with epithelial ovarian cancer (EOC). However, the effectiveness of this treatment depend on various elements e.g. type of operation. It is accepted that optimal surgery correlates with longer survival of patients. The other element, an efficiency of immune system after surgical intervention although important is less elucidated. The aim of this study was to establish the impact of optimal and sub-optimal operation on immunological status of EOC patients regarding also their overall survival (OS). On the day of primary cytoreduction and 7days after, the selected serum immunological parameters were determined in 49 patients with confirmed EOC. We found that, the level of immunosuppressive (interleukin 10; transforming growth factor-β - TGF-β1) and pro-inflammatory (interleukin-6 and 8) cytokines was significantly higher in the group of patients with advanced stage of disease, compared to early stage. However, the number of circulating CD3, CD4 or CD8 cells, CD19 and NK cells was similar in both group of EOC patients. The overall survival of patients who underwent optimal cytoreduction was significantly higher than that in whom only sub-optimal surgery was performed. Sub-optimal cytoreduction only partially weakened the serum level of TGF-β1 and IL-8 and what is more enhanced the number of circulating CD4CD25 cells in patients with advanced stage of disease. Sub-optimal surgery and high post-operative level of TGF-β1 increased the hazard ratio for patients. Besides, we noticed that the high pre-operative concentration of TGF-β1 could distinguish all EOC patients (independently of FIGO classification) for whom optimal or sub-optimal surgery would be applied. Sub-optimal debulking resulted in higher immunosuppression and lower OS of EOC patients.

摘要

初次肿瘤细胞减灭术联合化疗是上皮性卵巢癌(EOC)患者的标准治疗方法。然而,这种治疗的有效性取决于多种因素,例如手术类型。公认的是,最佳手术与患者更长的生存期相关。另一个因素,手术干预后免疫系统的效率虽然很重要,但却较少被阐明。本研究的目的是确定最佳和次最佳手术对EOC患者免疫状态的影响以及他们的总生存期(OS)。在初次肿瘤细胞减灭术当天及术后7天,对49例确诊为EOC的患者测定了选定的血清免疫参数。我们发现,与早期疾病患者相比,晚期疾病患者组中免疫抑制性(白细胞介素10;转化生长因子-β - TGF-β1)和促炎性(白细胞介素-6和8)细胞因子的水平显著更高。然而,两组EOC患者中循环CD3、CD4或CD8细胞、CD19和NK细胞的数量相似。接受最佳肿瘤细胞减灭术的患者的总生存期显著高于仅接受次最佳手术的患者。次最佳肿瘤细胞减灭术仅部分削弱了TGF-β1和IL-8的血清水平,而且增加了晚期疾病患者循环CD4CD25细胞的数量。次最佳手术和术后高TGF-β1水平增加了患者的风险比。此外,我们注意到术前高浓度的TGF-β1可以区分所有EOC患者(独立于国际妇产科联盟(FIGO)分类),对于这些患者将应用最佳或次最佳手术。次最佳肿瘤细胞减灭术导致EOC患者更高的免疫抑制和更低的总生存期。

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