Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis
- Chenggong Tu
- Yongjiang Zheng
- Hui Zhang
- Jinheng Wang
Affiliations: 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
- Published online on: April 21, 2020 https://doi.org/10.3892/or.2020.7587
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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.