Calgarotto Andrana K, Longhini Ana L, Pericole de Souza Fernando V, Duarte Adriana S Santos, Ferro Karla P, Santos Irene, Maso Victor, Olalla Saad Sara T, Torello Cristiane Okuda
University of Campinas, Campinas, São Paulo, Brazil.
Integr Cancer Ther. 2021 Jan-Dec;20:15347354211002647. doi: 10.1177/15347354211002647.
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.
对绿茶（GT）治疗进行了评估，以观察其对患有骨髓发育异常相关改变的老年急性髓系白血病患者（AML-MRC）免疫和抗肿瘤反应的影响，这些患者不符合接受积极化疗和骨髓移植的条件。参与该研究的符合条件的患者（n = 10）单独口服GT提取物（1000毫克/天）或与小剂量阿糖胞苷化疗联合使用，至少持续6个月和/或直至病情进展。每月对骨髓（BM）和外周血（PB）进行评估。与对照组相比，中位生存期有所延长，尽管无统计学差异。有趣的是，发现患者的免疫状况有所改善。30天后，检测到一种活化的细胞毒性表型：GT增加了总CD8 T细胞和幼稚/效应CD8 T细胞、穿孔素/颗粒酶B自然杀伤细胞、单核细胞以及经典单核细胞，并增加了活性氧（ROS）的产生。还观察到免疫抑制状况有所降低：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细胞中的ROS水平和CXCR4表达降低，活检组织中的核因子红细胞2相关因子2（NRF2）和缺氧诱导因子1α（HIF-1α）表达也降低。GT诱导的免疫调节似乎在摄入后30天就会出现，无论肿瘤负荷如何，并且即使在存在小剂量化疗的情况下也能维持长达180天。这项初步研究强调，GT提取物是安全的，并且可以改善老年AML-MRC患者的免疫系统。
