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Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes
Integrative Cancer Therapies ( IF 2.9 ) Pub Date : 2021-03-23 , DOI: 10.1177/15347354211002647
Andrana K Calgarotto 1 , Ana L Longhini 1 , Fernando V Pericole de Souza 1 , Adriana S Santos Duarte 1 , Karla P Ferro 1 , Irene Santos 1 , Victor Maso 1 , Sara T Olalla Saad 1 , Cristiane Okuda Torello 1
Affiliation  

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-β and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2–related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.



中文翻译:

绿茶联合小剂量化疗对老年急性髓系白血病伴骨髓增生异常相关变化的免疫调节作用

评估了绿茶 (GT) 治疗对不适合积极化疗和骨髓移植的患有骨髓增生异常相关变化 (AML-MRC) 的老年急性髓系白血病患者的免疫和抗肿瘤反应的影响。参加研究的合格患者(n = 10)接受单独口服剂量的 GT 提取物(1000 毫克/天)或联合低剂量阿糖胞苷化疗至少 6 个月和/或直至进展。每月评估骨髓 (BM) 和外周血 (PB)。与对照组相比,中位生存期增加,但没有统计学差异。有趣的是,发现患者的免疫学特征有所改善。30 天后,检测到激活的细胞毒性表型:GT 增加了总和初始/效应 CD8 +T 细胞、穿孔素+ /颗粒酶 B +自然杀伤细胞、单核细胞和具有增加的活性氧 (ROS) 产生的经典单核细胞。还观察到免疫抑制谱的降低:GT 降低了 TGF-β 和 IL-4 的表达,并降低了调节性 T 细胞和 CXCR4 +调节性 T 细胞的频率。骨髓 CD34 + 中ROS 水平和 CXCR4 表达降低细胞,以及核因子红细胞 2 相关因子 2 (NRF2) 和缺氧诱导因子 1α (HIF-1α) 在活检中的表达。无论肿瘤负荷如何,GT 诱导的免疫调节似乎在摄入后 30 天就会发生,并维持长达 180 天,即使在低剂量化疗的情况下也是如此。这项初步研究强调 GT 提取物是安全的,可以改善老年 AML-MRC 患者的免疫系统。

更新日期:2021-03-23
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