Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high-dimensional single-cell analysis
Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high-dimensional single-cell analysis
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DOI：
10.3892/or.2020.7587
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发表时间：
2020-04
期刊：
影响因子：
4.2
通讯作者：
C. Tu;Yongjiang Zheng;Hui Zhang;Jinheng Wang
中科院分区：
文献类型：
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作者：
C. Tu;Yongjiang Zheng;Hui Zhang;Jinheng Wang
免疫检查点封锁使患者在征服癌症方面取得了无与伦比的成功。不幸的是，个体间的异质性导致许多患者无法控制肿瘤。新兴的质量细胞术技术能够揭示一种多尺度的肿瘤免疫格局，从而提高癌症免疫治疗的疗效。我们采用质量细胞术检测了3例多发性骨髓瘤、淀粉样轻链淀粉样变性、孤立性骨浆细胞瘤患者和1例非血液病患者的骨髓和外周血中的个性化免疫检查点状态。同时检测了18种免疫调节受体和配体在17个确定的细胞群体上的表达。通过单细胞分析，我们确定了作为免疫抑制信号源的T细胞簇，揭示了个体完整的免疫检查点轴线，从而为每个患者提供了多个潜在的免疫治疗靶点，包括程序性细胞死亡蛋白1(PD-1)、可诱导共刺激因子(ICOS)和分化簇28(CD28)。区分作为免疫检查点信号的提供者和接收者的细胞群体，证明了个体中免疫调节信号的明显交叉相互作用网络。这些深入的个性化数据表明，质量细胞术是一项强大的创新，可以发现原发和周围肿瘤微环境中的系统免疫状态。
Immune checkpoint blockade endows patients with unparalleled success in conquering cancer. Unfortunately, inter-individual heterogeneity causes failure in controlling tumors in many patients. Emerging mass cytometry technology is capable of revealing a multiscale onco-immune landscape that improves the efficacy of cancer immunotherapy. We introduced mass cytometry to determine the personalized immune checkpoint status in bone marrow and peripheral blood samples from 3 patients with multiple myeloma, amyloid light-chain amyloidosis, and solitary bone plasmacytoma and 1 non-hematologic malignancy patient. The expression of 18 immune regulatory receptors and ligands on 17 defined cell populations was simultaneously examined. By single-cell analyses, we identified the T cell clusters that serve as immunosuppressive signal source and revealed integrated immune checkpoint axes of individuals, thereby providing multiple potential immunotherapeutic targets, including programmed cell death protein 1 (PD-1), inducible co-stimulator (ICOS), and cluster of differentiation 28 (CD28), for each patient. Distinguishing the cell populations that function as providers and receivers of the immune checkpoint signals demonstrated a distinct cross-interaction network of immunomodulatory signals in individuals. These in-depth personalized data demonstrate mass cytometry as a powerful innovation to discover the systematical immune status in the primary and peripheral tumor microenvironment.