Identification of the immune checkpoint signature of multiple myeloma using mass cytometry‐based single‐cell analysis

Abstract

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.

Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system

“…Since bilirubin significantly improves atherosclerosis which is closely associated with the immune response, it is likely that bilirubin also has an effect on the immune system. Thus, we used a high-throughput single cell technology, mass cytometry [ 31 , 35 ], to simultaneously measure the expression of 26 markers on immune cells from the spleen or peripheral blood at the single cell level. ViSNE analysis of CD45 + cells from the spleen was performed to visualize these high-dimensional mass cytometry data in two dimensions.…”

“…Atherosclerosis is a disease associated with inflammation that relies heavily on the immune system for its development and modulation [ 28 ]. New high-throughput single cell technologies, such as mass cytometry and single-cell RNA sequencing, enable a comprehensive analysis of the immune system during atherosclerosis progression through uncovering the diversity of > 15 immune cell populations [ 29 – 31 ]. The dissection of immune modulation has greatly contributed to the understanding of atherosclerosis mechanisms and has provided novel insights into its treatment via immune therapy.…”

Comprehensive Analysis of m6A RNA Methylation Regulators in the Prognosis and Immune Microenvironment of Multiple Myeloma

“…Next, we studied the expression of HLA system and immune checkpoints, including CD274 (PD-L1), PDCD1LG2, VTCN1 (v-set domain-containing T cell activation inhibitor), CD276, and IDO1 (indoleamine 2,3-dioxygenase 1) ( 37 ), which were found on the surfaces of cells to help the recognition of immune system and involved in the immune activation and inhibition. We observed that the HLA family, including HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DPB2, HLA-DQA1, HLA-DQB1, HLD-DRA, HLA-DRB1, HLA-DRB6, and HLA-E, showed significant decrease in high-risk group ( Figure 8A ).…”

Endocytic pathway inhibition attenuates extracellular vesicle-induced reduction of chemosensitivity to bortezomib in multiple myeloma cells

“…BMMCs were isolated from the BM cells of MM patients and then cultured with DID-labeled sEVs in the presence of dynasore. As the loss of CD138 during cold storage and processing frequently occurs 34 , 35 , cells with a CD38 high CD45 -/dim phenotype were defined as malignant MM cells and rest of CD45 + cells were considered as healthy immune cells (Figure 7 A). Without dynasore treatment, DID signal in MM cells was stronger than that in immune cells after the co-culture of BMMCs with DID-labeled sEVs (Figure 7 A-B).…”