Abstract：
Tregs are able of suppressing tumor-specific effector cells, such as lymphocytes CD8+, CD4+ and Natural Killer cells. Different drugs, especially different schedules of administration, like metronomic chemotherapy (mCHT), seem to be able to increase anticancer immunity, by acting on downregulation of Tregs. Most of the data available regarding the immunomodulating effect of mCHT have been obtained with Cyclophosphamide (CTX). Aim of the present study was to explore the effects of mVRL and mCAPE administration, alone or in combination, on T cells. Observation of 13 metastatic breast cancer patients lasted controlling for 56 days, where Treg frequencies and function, spontaneous anti-tumor T-cell responses were monitored, as well as the clinical outcome. No depletion in Treg absolute numbers, or percentage of T lymphocytes, was observed. Only in 5 patients, a modest and transient depletion of Tregs was observed during the first 14 days of treatment. To better describe the effect on Tregs, we subsequently looked at the variations in Memory, Naïve and Activated Treg subpopulations: we observed a trend in reduction for memory Treg (Treg MEM) and an increase for Treg Naïve (Treg NAIVE) and Treg Activated (Treg ACT) components. We finally analyzed the average trend of Treg in the Treg depleted patients and non-depleted ones, without fiding any significant differences. The trend of the Treg MEM appeared different, showing a reduction during the first 14 days, followed by an increase at the levels before treatment at Day 56 in the group of depleted patients and a progressive substantial reduction in the group of non-depleted patients along the entire course of treatment. Opposed to the data known, treatment with mVRL w/o mCAPE did not show any effect on Tregs.
摘要：
Tregs能够抑制肿瘤特异性效应细胞，如淋巴细胞CD8+，CD4+和自然杀伤细胞。不同的药物,尤其是不同的管理时间表，像节拍化疗（mCHT），似乎能够增加抗癌免疫力，通过下调Tregs的监管。关于mCHT的免疫调节作用的可获得的大多数数据已经用环磷酰胺(CTX)获得。本研究的目的是探索mVRL和mCAPE管理的效果，单独或组合，在T细胞上。观察13例转移性乳腺癌患者持续控制56天，其中Treg频率和功能，监测自发的抗肿瘤T细胞反应，以及临床结果。Treg绝对数量没有耗尽，或T淋巴细胞的百分比，被观察到。仅在5名患者中，在治疗的前14天观察到Tregs的适度和短暂消耗.为了更好地描述对Tregs的影响，我们随后研究了记忆中的变化，幼稚和激活的Treg亚群：我们观察到记忆Treg（TregMEM）减少的趋势以及Treg幼稚（TregNAIVE）和Treg激活（TregACT）成分的增加。我们最终分析了Treg耗尽患者和未耗尽患者中Treg的平均趋势，没有任何重大差异。TregMEM的趋势出现了不同，在前14天显示减少，随后在第56天，耗竭患者组中的治疗前水平增加，而在整个治疗过程中，非耗竭患者组中的逐渐大幅减少。与已知的数据相反，用mVRLw/omCAPE治疗对Tregs没有任何影响。
