Awwad Mohamed H S, Kriegsmann Katharina, Plaumann Julian, Benn Michael, Hillengass Jens, Raab Marc S, Bertsch Uta, Munder Markus, Weisel Katja, Salwender Hans Jürgen, Hänel Mathias, Fenk Roland, Dürig Jan, Müller-Tidow Carsten, Goldschmidt Hartmut, Hundemer Michael
Department of Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
National Center for Tumour Diseases, University of Heidelberg, Heidelberg, Germany.
Oncoimmunology. 2018 Aug 1;7(10):e1486356. doi: 10.1080/2162402X.2018.1486356. eCollection 2018.
: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. : We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined observations with assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. : We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. : In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.
虽然最近的研究描述了IKZF1/3蛋白在多发性骨髓瘤（MM）细胞中的作用，但很少有研究强调IKZF1/3在T细胞中表达的重要性。在本研究中，我们检测了III期MM患者T细胞中IKZF1/3表达的预后和预测价值。
我们根据Durie-Salmon分期系统，通过流式细胞术分析了45例I期MM（MMI）和50例新诊断的III期MM（MMIII）患者T细胞中的IKZF1/3表达水平，以检测其预后和预测价值。我们还结合观察结果与检测方法，以确定IKZF1/3表达对162例MMIII患者T细胞免疫表型和抗肿瘤T细胞反应的影响。
我们发现，在接受免疫调节药物（沙利度胺、来那度胺和泊马度胺）治疗的MMIII患者中，T细胞中高表达IKZF3而非IKZF1与较好的总生存期相关。此外，我们表明T细胞中较高的IKZF3表达会抑制骨髓瘤特异性T细胞反应，并且高IKZF3表达患者的免疫表型显示出与免疫调节药物诱导的变化相反的特征。虽然我们观察到MMIII患者T细胞中的IKZF3表达水平高于MMI患者，但IKZF3表达不受肿瘤微环境的影响。
总之，T细胞中IKZF3的表达对接受免疫调节药物治疗的MMIII患者的临床结局具有预测价值，因为它对T细胞功能有深远的调节作用。
