白血病
髓系白血病
癌症研究
肿瘤微环境
免疫疗法
免疫学
CXCR4型
CD8型
造血
医学
生物
免疫系统
趋化因子
干细胞
细胞生物学
作者
Rong Wang,Wenli Feng,Hao Wang,Lina Wang,Xiao Yang,Feifei Yang,Yingchi Zhang,Xiaoli Liu,Dongyue Zhang,Qian Ren,Xiaoming Feng,Guoguang Zheng
标识
DOI:10.1016/j.canlet.2019.10.032
摘要
Blocking the migration of regulatory T cells (Tregs) to the tumor microenvironment is a promising strategy for tumor immunotherapy. Treg accumulation in the leukemic hematopoietic microenvironment (LHME) has adverse impacts on patient outcomes. The mechanism and effective methods of disrupting Treg accumulation in the LHME have not been well established. Here, we studied the distribution and characteristics of Tregs in the LHME, investigated the effects of Treg ablation on leukemia progression, explored the mechanisms leading to Treg accumulation, and studied whether blocking Treg migration to the LHME delayed leukemia progression in MLL-AF9-induced mouse acute myeloid leukemia (AML) models using wildtype (WT) and Foxp3DTR/GFP mice. Increased accumulation of more activated Tregs was detected in the LHME. Inducible Treg ablation prolonged the survival of AML mice by promoting the antileukemic effects of CD8+ T cells. Furthermore, both local expansion and migration accounted for Treg accumulation in the LHME. Moreover, blocking the CCL3-CCR1/CCR5 and CXCL12-CXCR4 axes inhibited Treg accumulation in the LHME and delayed leukemia progression. Our findings provide laboratory evidence for a potential leukemia immunotherapy by blocking the migration of Tregs.
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