Abstract A224: Bone marrow T-cells are tumor-infiltrating T-cells in pediatric patients with acute leukemia and their phenotype reflects immune evasion of leukemic blasts
Semjon Willier, Paula Rothaemel, Jonas Wilhelm, D. Stenger, Theresa Käuferle, I. Schmid, M. Albert, V. Binder, F. Blaeschke, T. Feuchtinger
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引用次数: 0
Abstract
Object: Acute leukemia is the most common malignancy in children. Despite recent therapeutic advances patients with relapsed or refractory disease require new treatment options. While synthetic immunotherapies such as chimeric antigen receptor (CAR) T-cells have shown impressive efficacy in B-precursor acute lymphoblastic leukemia (BCP-ALL) patients, the interaction between leukemic blasts and bone marrow T-cells remains largely unknown. Therefore, the role for immune response amplifiers in leukemia patients is currently unclear. Leukemia outgrowth leads to low frequency of physiologic bone marrow populations such as T-cells. Those T-cells are consequently within the site of tumor development and can thus be defined as tumor-infiltrating lymphocytes (TILs). Dysfunction of TILs has been described in a variety of solid and in some hematologic malignancies. To determine the changes driven by leukemia blasts we analyzed T-cells in bone marrow samples from pediatric patients with BCP-ALL, T-precursor ALL (TCP-ALL) and acute myelogenous leukemia (AML) at the time of diagnosis and relapse in comparison to healthy bone marrow donors. Material and Methods: In pilot experiments, any artificial changes in marker expression due to cryopreservation and thawing were excluded (n=5). Then, cryopreserved bone marrow samples from both pediatric patients with acute leukemia (n= 77; BCP-ALL: 18, TCP-ALL: 23, AML: 36) and age-matched healthy bone marrow donors (n=23) were identified in our local biobank. Multicolor flow cytometry was performed to quantify co-inhibitory markers on CD4 and CD8 T-cells in primary (n=49) and relapse leukemia samples (n=28). Results: The frequency of bone marrow T-cells was reduced in patients with acute leukemia in comparison with healthy controls (5.9% vs. 24.4%, mean values, p primary > healthy). These findings could reflect insufficient immune surveillance of pediatric leukemia by bone marrow T-cells and may provide a rationale for future therapeutic interventions. Citation Format: Semjon Manuel Willier, Paula Rothaemel, Jonas Wilhelm, Dana Stenger, Theresa Kauferle, Irene Schmid, Michael H. Albert, Vera Binder, Franziska Blaeschke, Tobias Feuchtinger. Bone marrow T-cells are tumor-infiltrating T-cells in pediatric patients with acute leukemia and their phenotype reflects immune evasion of leukemic blasts [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A224.
目的:急性白血病是儿童最常见的恶性肿瘤。尽管最近的治疗进展,复发或难治性疾病的患者需要新的治疗选择。虽然嵌合抗原受体(CAR) t细胞等合成免疫疗法在b前体急性淋巴细胞白血病(BCP-ALL)患者中显示出令人印象深刻的疗效,但白血病母细胞和骨髓t细胞之间的相互作用在很大程度上仍然未知。因此,免疫反应放大器在白血病患者中的作用目前尚不清楚。白血病的生长导致生理性骨髓群体(如t细胞)的低频率。这些t细胞因此在肿瘤发生的部位,因此可以被定义为肿瘤浸润淋巴细胞(til)。til功能障碍已在多种实体和一些血液恶性肿瘤中被描述。为了确定白血病原细胞驱动的变化,我们分析了BCP-ALL、t前体ALL (TCP-ALL)和急性髓性白血病(AML)患儿在诊断和复发时的骨髓样本中的t细胞,并与健康骨髓供者进行了比较。材料和方法:在中试实验中,排除了任何因冷冻和解冻而导致的标记物表达的人为变化(n=5)。然后,冷冻保存的骨髓样本分别来自急性白血病患儿(n= 77;BCP-ALL: 18, TCP-ALL: 23, AML: 36)和年龄匹配的健康骨髓供者(n=23)在我们当地的生物库中被发现。采用多色流式细胞术定量原发性(n=49)和复发性白血病(n=28)患者CD4和CD8 t细胞的共抑制标志物。结果:急性白血病患者骨髓t细胞频率较健康对照降低(5.9% vs. 24.4%,平均值,p原发>健康)。这些发现可能反映了骨髓t细胞对儿童白血病的免疫监测不足,并可能为未来的治疗干预提供理论依据。引文格式:Semjon Manuel willer, Paula Rothaemel, Jonas Wilhelm, Dana Stenger, Theresa Kauferle, Irene Schmid, Michael H. Albert, Vera Binder, Franziska Blaeschke, Tobias Feuchtinger。骨髓t细胞是儿童急性白血病患者的肿瘤浸润t细胞,其表型反映了白血病母细胞的免疫逃避[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫,2019;7(2增刊):摘要nr A224。