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术前皮下注射白细胞介素-2可消除可手术癌症患者手术诱导的循环树突状细胞减少。

Abrogation of surgery-induced decline in circulating dendritic cells by subcutaneous preoperative administration of IL-2 in operable cancer patients.

作者信息

Brivio F, Lissoni P, Gilardi R, Ferrante R, Vigore L, Curzi L, Uggeri F, Nespoli A, Fumagalli L

机构信息

Third Surgery Division, San Gerardo Hospital, Monza, Milano, Italy.

出版信息

J Biol Regul Homeost Agents. 2000 Jul-Sep;14(3):200-3.

Abstract

Surgery-induced immunosuppression is characterized by a decline in lymphocyte count, particularly T lymphocyte number. In addition, preliminary studies have shown that the postoperative period is also characterized by a decline in the number of circulating dendritic cells (DC), whose fundamental anticancer role has been recently demonstrated. Previous studies had already shown that the preoperative injection of IL-2 may completely abrogate surgery-induced lymphocytopenia, whereas its eventual influence on DC system during the perioperative period is still unknown. The present study was performed to evaluate the influence of IL-2 preoperative immunotherapy on the perioperative changes in circulating DC number in patients affected by colorectal cancer. The study included 14 consecutive patients, who were randomized to be treated with or without IL-2 presurgical immunotherapy (12 million IU/day for 3 days subcutaneously). Circulating immature and mature cells were evaluated before surgery and at days 3 and 7 of the postoperative period. The detection was made by FACS using monoclonal antibodies against CD123 and CD11c to recognize immature and mature DC, respectively. Surgery induced a significant decline in the mean number of both immature and mature DC. The pre-surgical administration of IL-2 completely abrogated surgery-induced decline in immature DC cell amount. Moreover, mature DC mean number was diminished only at day 3 of the postoperative period, since the value observed at day 7 was not significantly lower than that found before surgery. This preliminary study shows that surgery-induced immunosuppression is characterized also by a significant decline in the mean number of both immature and mature DC. Moreover, this study would suggest that the preoperative immunotherapy with IL-2 may counteract surgery-induced failure of DC system. Because of the fundamental antitumor role of DC, this evidence could have a prognostic impact on the clinical course of the neoplastic disease.

摘要

手术诱导的免疫抑制的特征是淋巴细胞计数下降,尤其是T淋巴细胞数量减少。此外,初步研究表明,术后阶段的特征还包括循环树突状细胞(DC)数量的下降,其重要的抗癌作用最近已得到证实。先前的研究已经表明,术前注射白细胞介素-2(IL-2)可能完全消除手术诱导的淋巴细胞减少,而其在围手术期对DC系统的最终影响仍然未知。本研究旨在评估IL-2术前免疫疗法对结直肠癌患者围手术期循环DC数量变化的影响。该研究纳入了14例连续患者,他们被随机分为接受或不接受术前IL-2免疫疗法(皮下注射1200万国际单位/天,共3天)。在手术前以及术后第3天和第7天评估循环中的未成熟和成熟细胞。通过流式细胞术(FACS)使用分别针对CD123和CD11c的单克隆抗体来识别未成熟和成熟DC进行检测。手术导致未成熟和成熟DC的平均数量均显著下降。术前给予IL-2完全消除了手术诱导的未成熟DC细胞数量的下降。此外,成熟DC的平均数量仅在术后第3天减少,因为在第7天观察到的值并不显著低于手术前的值。这项初步研究表明,手术诱导的免疫抑制的特征还在于未成熟和成熟DC的平均数量均显著下降。此外,本研究表明术前使用IL-2进行免疫疗法可能抵消手术诱导的DC系统功能障碍。由于DC的重要抗肿瘤作用,这一证据可能对肿瘤疾病的临床进程产生预后影响。

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