Rico M J, Rozados V R, Mainetti L E, Zacarias Fluck M F, Matar P, Scharovsky O G
Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, Rosario 2000, Argentina.
Exp Oncol. 2012;34(1):38-42.
Experimental and clinical studies showed that the administration of cyclophosphamide (Cy) in low doses leads to an enhancement of the antitumor immune response. Our objective was to study the modulation, if any, by low dose Cy, of T regulatory (Treg) and natural killer T (NKT) I cells, two cell populations of the innate immune response with opposing effects on the tumors, in a rat B cell lymphoma model.
Inbred e rats were challenged s.c. with L-TACB lymphoma and on day 14 animals were distributed in two groups. Treated: injected i.p. with cyclophosphamide (10mg/kg of body weight) and
injected i.p. with saline. Blood samples were taken from days 0 to 21 and the percentage of T regulatory and natural killer T I cells were determined by flow cytometry.
We found that the increase of natural and inducible T regulatory cells of peripheral blood achieved during tumor growth was significantly downregulated by cyclophosphamide. On the contrary, natural killer T I cells were not modulated by the treatment.
The antimetastatic effect of a single low dose of Cy would be due, at least in part, to downregulation of natural and inducible T regulatory cells.
实验和临床研究表明,低剂量环磷酰胺(Cy)给药可增强抗肿瘤免疫反应。我们的目的是在大鼠B细胞淋巴瘤模型中研究低剂量Cy对调节性T细胞(Treg)和自然杀伤T(NKT)I细胞的调节作用(若有),这两种先天免疫反应细胞群体对肿瘤具有相反的作用。
将近交系大鼠皮下接种L-TACB淋巴瘤,在第14天,将动物分为两组。治疗组:腹腔注射环磷酰胺(10mg/kg体重);对照组:腹腔注射生理盐水。在第0至21天采集血样,通过流式细胞术测定调节性T细胞和自然杀伤T I细胞的百分比。
我们发现,肿瘤生长期间外周血中天然和诱导性调节性T细胞的增加被环磷酰胺显著下调。相反,自然杀伤T I细胞未受该治疗的调节。
单次低剂量Cy的抗转移作用至少部分归因于天然和诱导性调节性T细胞的下调。