Iannone Francesco, Porzia Alessandra, Peruzzi Giovanna, Birarelli Patrizia, Milana Bernardina, Sacco Luca, Dinatale Giuseppe, Peparini Nadia, Prezioso Giampaolo, Battella Simone, Caronna Roberto, Morrone Stefania, Palmieri Gabriella, Mainiero Fabrizio, Chirletti Piero
From the *Section of Interdisciplinary Surgery F. Durante, Department of Surgical Sciences, †Department of Molecular Medicine, ‡Istituto Italiano di Tecnologia, CLNS, and §Department of Experimental Medicine, Sapienza University of Rome, Italy.
Pancreas. 2015 Apr;44(3):386-93. doi: 10.1097/MPA.0000000000000288.
Tumor burden and invasiveness establish a microenvironment that surgery could alter. This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy.
Lymphocyte frequency and natural cytotoxicity were evaluated by flow cytometry and in vitro assay on peripheral blood from initial and advanced-stage pancreatic cancer patients before (BS), at day 7 (PS7), and at day 30 (PS30) after surgery.
An increase in natural killer (NK) cells and the diminution of B-cells occurred at PS30, whereas cytotoxicity decreased at PS7. The positive correlation between NK frequency and cytotoxicity at BS and PS7 revealed an altered NK behavior. The elevation of NK cell frequency at PS30, an initial defect in CD56bright NK, and the aberrant correlation between NK frequency and cytotoxicity remained significant in advanced-stage patients, whereas the diminution of NK cytotoxicity only affected initial stage patients.
The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.
肿瘤负荷和侵袭性形成了一种手术可能改变的微环境。本研究对十二指肠胰切除术之前及术后不同时间点的胰腺癌患者外周淋巴细胞亚群的大小、动态变化及功能进行了全面分析。
通过流式细胞术和体外试验,对初诊及晚期胰腺癌患者手术前(BS)、术后第7天(PS7)和第30天(PS30)外周血中的淋巴细胞频率和自然细胞毒性进行评估。
PS30时自然杀伤(NK)细胞增加,B细胞减少,而PS7时细胞毒性降低。BS和PS7时NK频率与细胞毒性之间的正相关揭示了NK行为的改变。PS30时NK细胞频率升高、CD56bright NK细胞最初存在缺陷以及NK频率与细胞毒性之间的异常相关性在晚期患者中仍然显著,而NK细胞毒性降低仅影响早期患者。
术前患者的NK细胞功能能力发生改变;十二指肠胰切除术与NK功能的短期损害以及长期NK细胞增加和异常NK行为的逆转有关,这可能会影响对残留癌症的免疫监视。