Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment
Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment
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DOI：
10.1111/ejh.12228
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发表时间：
2014-03-01
影响因子：
3.1
通讯作者：
Blank, Christian U.
中科院分区：
文献类型：
--
作者：
Kroenig, Holger;Kremmler, Lukas;Blank, Christian U.
虽然目前治疗急性髓细胞白血病的特点是高反应率，但由于经常复发和老年患者不适合干细胞移植，患者的长期结局仍然令人失望。因此，人们已经做出了相当大的努力，将免疫治疗方法纳入急性髓系白血病（AML）巩固治疗中，但迄今为止的临床效果令人失望。B7家族配体程序性死亡受体配体1（PD-L1，B7-H1，CD 274）最近已被描述（结果相互矛盾）在AML母细胞上表达，并与T细胞上的受体程序性死亡受体-1相互作用（PD-1，CD 279），已经显示抑制T细胞功能并允许动物模型中休眠的AML细胞存活。我们分析了来自健康供体和AML患者的新鲜分离的髓样前体细胞在治疗期间不同时间点有或没有干扰素暴露的PD-L1表达。我们发现IFN-γ诱导的PD-L1表达在初始治疗后最为显著，并且与治疗结果无关。介导的适应性免疫耐药性，并主张在AML治疗的巩固阶段靶向PD-L1/PD-1通路。
IntroductionWhile current treatment for acute myeloid leukemia is characterized by high response rates, patients' long-term outcome is still disappointing, due to frequent relapse and ineligibility of the often elderly patients for stem cell transplantation approaches. Considerable efforts have, thus, been made to incorporate immunotherapeutic approaches in the acute myeloid leukemia (AML) consolidation, with so far disappointing clinical benefit. The B7 family ligand programmed-death receptor-ligand 1 (PD-L1, B7-H1, CD274) has been recently described (with conflicting results) to be expressed on AML blast cells, and interaction with its receptor on T cells, programmed death receptor-1 (PD-1, CD279), has been shown to suppress T-cell functions and to allow survival of dormant AML cells in animal models.Design and MethodsIn this work, we analyzed freshly isolated myeloid precursor cells from healthy donors and from AML patients for PD-L1 expression with or without interferon- exposure at different time points during their treatment.ResultsWhile without IFN exposure, only minor differences were observed, we found IFN--induced PD-L1 expression most prominent after initial treatment and independent of treatment outcome.ConclusionsOur observations support the recently suggested PD-L1-mediated adaptive immune resistance and argue for a targeting of the PD-L1/PD-1 pathway during the consolidation phase of AML treatment.