Blocking migration of regulatory T cells to leukemic hematopoietic microenvironment delays disease progression in mouse leukemia model
Blocking migration of regulatory T cells to leukemic hematopoietic microenvironment delays disease progression in mouse leukemia model
复制标题
在小鼠白血病模型中，阻断调节性 T 细胞向白血病造血微环境的迁移可延缓疾病进展。
DOI：
10.1016/j.canlet.2019.10.032
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发表时间：
2020-01-01
期刊：
影响因子：
9.7
通讯作者：
Zheng, Guoguang
中科院分区：
文献类型：
--
作者：
Wang, Rong;Feng, Wenli;Zheng, Guoguang
阻断调节性T细胞（TCFs）向肿瘤微环境的迁移是肿瘤免疫治疗的一种有前途的策略。白血病造血微环境（LHME）中Treg的积累对患者结局有不利影响。在LHME中破坏Treg积累的机制和有效方法尚未很好地建立。在这里，我们研究了THE 3在LHME中的分布和特征，研究了Treg消融对白血病进展的影响，探索了导致Treg积累的机制，并研究了阻断Treg迁移到LHME是否延迟了MLL-AF 9诱导的小鼠急性髓性白血病（AML）模型中的白血病进展，使用野生型（WT）和Foxp 3（DTR/GFP）小鼠。在LHME中检测到更多活化的TdR的积累增加。诱导性Treg消融通过促进CD 8（+）T细胞的抗白血病作用延长AML小鼠的生存期。此外，局部扩张和迁移都是LHME中Treg积累的原因。此外，阻断CCL 3-CCR 1/CCR 5和CXCL 12-CXCR 4轴可抑制LHME中Treg的积累并延迟白血病进展。我们的研究结果为通过阻断TdR的迁移来进行潜在的白血病免疫治疗提供了实验室证据。
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 Foxp3(DTR/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.