Identification of the immune checkpoint signature of multiple myeloma using mass cytometry-based single-cell analysis
Identification of the immune checkpoint signature of multiple myeloma using mass cytometry-based single-cell analysis
复制标题
使用基于质谱流式细胞术的单细胞分析鉴定多发性骨髓瘤的免疫检查点特征
DOI：
10.1002/cti2.1132
复制
发表时间：
2020-05-01
影响因子：
5.8
通讯作者：
Liu，Jinbao
中科院分区：
文献类型：
--
作者：
Wang，Jinheng;Zheng，Yongjiang;Liu，Jinbao
目的为提高多发性骨髓瘤(MM)免疫检查点免疫治疗的成功率，需要新的靶点或策略。然而，MM微环境中的免疫检查点信号尚未完全阐明。在这里，我们的目的是全面了解MM微环境中不同的免疫亚群及其免疫检查点状态，为MM患者的治疗提供新的免疫治疗靶点。方法采用质量细胞术对MM患者和健康对照组的骨髓样本进行免疫检查点分析。结果发现MM患者免疫细胞组成异常，表现为活化的CD4T、CD8T、CD8+自然杀伤T样细胞和NK细胞数量显著增加。我们的数据表明多发性骨髓瘤细胞和免疫检查点表型之间存在相关性，并扩大了多发性骨髓瘤免疫特征的研究范围。MM患者骨髓和免疫效应细胞上的程序性细胞死亡1(PD-1)/PD配体2、Galectin-9/T细胞免疫球蛋白粘蛋白-3、诱导性T细胞共刺激因子(ICOS)/ICOS配体等几个关键免疫检查点和大量缺乏CD28的活化PD-1+CD8 T细胞被区分开来。对免疫格局的分析增强了我们对MM免疫环境的理解，并为改进基于免疫检查点阻断的MM免疫治疗提出了新的靶点。
ObjectivesNew targets or strategies are needed to increase the success of immune checkpoint‐based immunotherapy for multiple myeloma (MM). However, immune checkpoint signals in MM microenvironment have not been fully elucidated. Here, we aimed to have a broad overview of the different immune subsets and their immune checkpoint status, within the MM microenvironment, and to provide novel immunotherapeutic targets to treat MM patients.MethodsWe performed immune checkpoint profiling of bone marrow (BM) samples from MM patients and healthy controls using mass cytometry. With high‐dimensional single‐cell analysis of 30 immune proteins containing 10 pairs of immune checkpoint axes in 0.55 million of BM cells, an immune landscape of MM was mapped.ResultsWe identified an abnormality of immune cell composition by demonstrating a significant increase in activated CD4 T, CD8 T, CD8+natural killer T‐like and NK cells in MM BM. Our data suggest a correlation between MM cells and immune checkpoint phenotypes and expand the view of MM immune signatures. Specifically, several critical immune checkpoints, such as programmed cell death 1 (PD‐1)/PD ligand 2, galectin‐9/T‐cell immunoglobulin mucin‐3, and inducible T‐cell costimulator (ICOS)/ICOS ligand, on both MM and immune effector cells and a number of activated PD‐1+CD8 T cells lacking CD28 were distinguished in MM patients.ConclusionA clear interaction between MM cells and the surrounding immune cells was established, leading to immune checkpoint dysregulation. The analysis of the immune landscape enhances our understanding of the MM immunological milieu and proposes novel targets for improving immune checkpoint blockade‐based MM immunotherapy.