Objectives New 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. Methods We 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. Results We 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. Conclusion A 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.

中文翻译：

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使用基于大规模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。

目标 需要新的目标或策略来提高基于免疫检查点的免疫治疗多发性骨髓瘤 (MM) 的成功率。然而，MM 微环境中的免疫检查点信号尚未完全阐明。在这里，我们旨在对 MM 微环境中的不同免疫亚群及其免疫检查点状态有一个广泛的概述，并为治疗 MM 患者提供新的免疫治疗靶点。方法 我们使用质量细胞术对来自 MM 患者和健康对照的骨髓 (BM) 样本进行免疫检查点分析。通过对 55 万个 BM 细胞中包含 10 对免疫检查点轴的 30 种免疫蛋白进行高维单细胞分析，绘制了 MM 的免疫图谱。结果 我们通过证明 MM BM 中活化的 CD4 T、CD8 T、CD8+ 自然杀伤 T 样细胞和 NK 细胞显着增加，确定了免疫细胞组成的异常。我们的数据表明 MM 细胞与免疫检查点表型之间存在相关性，并扩展了 MM 免疫特征的观点。具体来说，两个关键的免疫检查点，如程序性细胞死亡 1 (PD-1)/PD 配体 2、半乳凝素 9/T 细胞免疫球蛋白粘蛋白 3 和诱导型 T 细胞共刺激物 (ICOS)/ICOS 配体MM 和免疫效应细胞以及许多缺乏 CD28 的活化 PD-1+ CD8 T 细胞在 MM 患者中有所区别。结论 MM细胞与周围免疫细胞之间建立了明显的相互作用，导致免疫检查点失调。