Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)
Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)
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DOI：
10.1182/blood-2011-09-377044
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发表时间：
2012-04-05
期刊：
影响因子：
20.3
通讯作者：
Craddock, Charles F.
中科院分区：
文献类型：
--
作者：
Goodyear, Oliver C.;Dennis, Mike;Craddock, Charles F.
增强GVL效应而不增加GVHD风险的策略是改善异基因干细胞移植（SCT）后的结果所必需的。阿扎胞苷（Azacitidine，AZA）在体外上调白血病原始细胞肿瘤抗原的表达，并在动物模型中增加免疫调节性T调节细胞（Immunomodulatory T regulatory cells，Tregulatory cells，Tregulatory cells，Tregulatory cells）的数量。AZA可能选择性地增强GVL效应，我们研究了同种异体SCT后AZA给药的免疫学后遗症。27例因急性髓性白血病接受了低强度异基因移植的患者接受了每月一次的AZA治疗，并测量了CD 8（+）T细胞对候选肿瘤抗原和循环T细胞的反应。移植后AZA耐受性良好，其给药与GVHD发生率低相关。与对照人群相比，AZA的给药增加了移植后前3个月内的THBG数量（P = 0.0127）。AZA给药还诱导了对几种肿瘤抗原的细胞毒性CD 8（+）T细胞应答，包括黑素瘤相关抗原1、B黑素瘤抗原1和Wilm肿瘤抗原1。这些数据支持移植后AZA作为增强GVL效应而不伴随GVHD增加的机制的进一步研究。该试验在http://isrctn.org上注册为#ISRCTN36825171。（血。2012;119（14）：3361-3369）
Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD. The trial was registered at http://isrctn.org as #ISRCTN36825171. (Blood. 2012;119(14):3361-3369)