Lissoni P, Tisi E, Brivio F, Barni S, Rovelli F, Perego M, Tancini G
Division of Radiation Oncology, San Gerardo Hospital, Milan, Italy.
Eur J Cancer. 1991;27(8):1014-6. doi: 10.1016/0277-5379(91)90271-e.
Both immunostimulatory and immunosuppressive events would occur during the immunotherapies of cancer, including interleukin 2 (IL-2) therapy. The marked increase in soluble IL-2 receptor (SIL-2R) levels during IL-2 therapy could represent a potentially negative biological effect, because of the receptor's capacity to bind IL-2 and compete for it with IL-2 cell surface receptor. Since it has been observed that macrophages stimulate in vitro the release of SIL-2R, a study was started to evaluate in vivo the role of macrophages in IL-2-induced SIL-2R rise by measuring neopterin, which is a marker of macrophage activity. The study included 9 advanced renal cancer patients, treated subcutaneously with IL-2 at 1.8 x 10(6) IU/m2 twice daily for 5 days/week for 6 weeks. Both SIL-2R and neopterin serum mean levels significantly increased during IL-2 treatment, and the highest concentrations were reached on the second week of therapy. SIL-2R rise was significantly correlated to that of neopterin. This study, by showing a positive correlation between SIL-2R and neopterin rise, would suggest a macrophage involvement in the stimulation of SIL-2R release during IL-2 immunotherapy of cancer.
在癌症免疫治疗期间,包括白细胞介素2(IL-2)治疗,免疫刺激和免疫抑制事件都会发生。在IL-2治疗期间,可溶性IL-2受体(SIL-2R)水平显著升高可能代表一种潜在的负面生物学效应,因为该受体能够结合IL-2并与IL-2细胞表面受体竞争。由于已经观察到巨噬细胞在体外刺激SIL-2R的释放,因此开展了一项研究,通过测量作为巨噬细胞活性标志物的新蝶呤来评估巨噬细胞在IL-2诱导的SIL-2R升高过程中的体内作用。该研究纳入了9例晚期肾癌患者,皮下注射IL-2,剂量为1.8×10(6)IU/m2,每天两次,每周5天,共6周。在IL-2治疗期间,SIL-2R和新蝶呤血清平均水平均显著升高,且在治疗的第二周达到最高浓度。SIL-2R升高与新蝶呤升高显著相关。这项研究通过显示SIL-2R与新蝶呤升高之间的正相关关系,提示在癌症的IL-2免疫治疗期间,巨噬细胞参与了SIL-2R释放的刺激过程。