Identification of potential immune-related mechanisms related to the development of multiple myeloma

• Published in: Chinese medical journal 2024-07, Vol.137 (13), p.1603-1613
• Main Authors: Wang, Yaomei, Zhang, Wenli, Li, Tiandong, Liu, Mengmeng, Gao, Mengya, Li, Xinqing, Chen, Yufei, Song, Yongping, Li, Wei, Du, Chunyan, Wang, Fang, Liu, Lina
• Format: Article
• Language: English
• Subjects: Bone marrow; Cells; Flow cytometry; Gene expression; Genomics; Lymphocytes; Multiple myeloma; Original; Software; Statistical analysis
• ISSN: 0366-6999; 2542-5641; 2542-5641
• DOI: 10.1097/CM9.0000000000003116

Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG + Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages are enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don't eat me"-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, especially the migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.