Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia.
Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia.
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DOI：
10.18632/oncotarget.7210
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发表时间：
2016-02-16
期刊：
影响因子：
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通讯作者：
Martner A
中科院分区：
文献类型：
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作者：
Sander FE;Rydström A;Bernson E;Kiffin R;Riise R;Aurelius J;Anderson H;Brune M;Foà R;Hellstrand K;Thorén FB;Martner A
在急性髓样白血病（AML）中，预防化疗后的复发仍然是一个挑战。在首次完全缓解中，在国际IV期试验（ClinicalTrials.gov; NCT01347996）中，首次完全缓解的八十四名非移植AML患者对组胺二氯化物和低剂量白介素-2接受了预防复发的免疫疗法。在免疫疗法周期中抽取血液样本，并分析血液中的CD8+（细胞毒性）T细胞表型。在治疗的第一个周期中，观察到细胞毒性T细胞的重新分布，包括减少T效应记忆细胞的减少和T效应细胞的增加。免疫疗法期间T细胞亚型的动力学预测性复发和存活，特别是在老年患者中，并且在校正潜在混杂因素后仍可以显着预测临床结果。与白血病相关抗原具有特异性的CD8+ T细胞的存在确定了较低的复发风险患者。我们的结果表明，T细胞介导的AML免疫监视的新方面，并在预防性免疫疗法中提供了可疑的生物标志物。
Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were drawn during cycles of immunotherapy and analyzed for CD8+ (cytotoxic) T cell phenotypes in blood. During the first cycle of therapy, a re-distribution of cytotoxic T cells was observed comprising a reduction of T effector memory cells and a concomitant increase of T effector cells. The dynamics of T cell subtypes during immunotherapy prognosticated relapse and survival, in particular among older patients and remained significantly predictive of clinical outcome after correction for potential confounders. Presence of CD8+ T cells with specificity for leukemia-associated antigens identified patients with low relapse risk. Our results point to novel aspects of T cell-mediated immunosurveillance in AML and provide conceivable biomarkers in relapse-preventive immunotherapy.