Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
Department of Hematology, The Third Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China.
Oncol Rep. 2020 Jul;44(1):224-240. doi: 10.3892/or.2020.7587. Epub 2020 Apr 21.
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.
免疫检查点阻断为患者征服癌症带来了前所未有的成功。不幸的是，个体间的异质性导致许多患者无法控制肿瘤。新兴的质谱流式细胞术能够揭示肿瘤免疫治疗的疗效改善的多尺度肿瘤免疫景观。我们引入质谱流式细胞术来确定 3 名多发性骨髓瘤、轻链淀粉样变性和孤立性骨浆细胞瘤患者以及 1 名非血液系统恶性肿瘤患者的骨髓和外周血样本中的个性化免疫检查点状态。同时检测了 17 个定义明确的细胞群中 18 个免疫调节受体和配体的表达。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，并揭示了个体的综合免疫检查点轴，从而为每位患者提供了多个潜在的免疫治疗靶点，包括程序性死亡蛋白 1（PD-1）、诱导共刺激因子（ICOS）和分化群 28（CD28）。区分作为免疫检查点信号提供者和接收者的细胞群，证明了个体中免疫调节信号的独特交叉相互作用网络。这些深入的个性化数据表明，质谱流式细胞术是一种强大的创新技术，可以发现原发性和外周肿瘤微环境中的系统免疫状态。
