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Assessment of the presence and anti-tumor potential of tumor-infiltrating lymphocytes in patients with acute myeloid leukemia

机译:急性髓细胞性白血病患者肿瘤浸润淋巴细胞的存在和抗肿瘤潜力的评估

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摘要

>Purpose: Assessing the possibility of finding tumor-infiltrating lymphocytes (TIL) in bone marrow of acute myeloid leukemia (AML) patients and evaluating the anti-tumor activity of these TIL against autologous AML cells.>Patients and methods: TIL were immunomagnetically isolated by using anti-CD3 from bone marrow samples of 20 patients at the presentation of AML or four weeks upon completion of chemotherapy. TIL were ex vivo expanded for two weeks and immunophenotyped. Functionality in terms of cytokine secretion and cytotoxicity was assessed by γ-interferon quantitation and Elispot assay, respectively.>Results: TIL were detected in bone marrow samples of 50% (10/20) of the patient cohort. They were noted to highly express CD137 and PD-1 and display a significantly higher anti-tumor reactivity compared to that of autologous peripheral blood lymphocytes. TIL could be expanded in co-cultures with irradiated feeder cells supplemented with interleukin (IL)-7 and IL-15.>Conclusion: Data suggested the presence of reactive γ-interferon-secreting TIL in AML patients. They are expandable and possess anti-tumor activity, which might have a great potential in the development of adoptive cellular therapy for AML.
机译:>目的:评估在急性髓细胞性白血病(AML)患者的骨髓中发现肿瘤浸润淋巴细胞(TIL)的可能性,并评估这些TIL对自体AML细胞的抗肿瘤活性。>患者和方法:在AML出现时或化疗完成后4周,使用抗CD3方法从20例患者的骨髓样品中免疫磁分离TIL。将TIL离体扩增两周并进行免疫表型。分别通过γ干扰素定量和Elispot分析评估细胞因子分泌和细胞毒性方面的功能。>结果:在患者队列的50%(10/20)的骨髓样本中检测到TIL。与自体外周血淋巴细胞相比,它们被高度表达CD137和PD-1,并显示出显着更高的抗肿瘤反应性。 TIL可以与辐照的饲养细胞一起补充白介素(IL)-7和IL-15一起扩增。>结论:数据表明AML患者存在反应性分泌γ-干扰素的TIL。它们可扩展并具有抗肿瘤活性,这可能在过继性AML细胞疗法的开发中具有巨大潜力。

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