Identification of potential immune-related mechanisms related to the development of multiple myeloma
10.1097/CM9.0000000000003116
- VernacularTitle:Identification of potential immune-related mechanisms related to the development of multiple myeloma
- Author:
Yaomei WANG
1
,
2
;
Wenli ZHANG
;
Tiandong LI
;
Mengmeng LIU
;
Mengya GAO
;
Xinqing LI
;
Yufei CHEN
;
Yongping SONG
;
Wei LI
;
Chunyan DU
;
Fang WANG
;
Lina LIU
Author Information
1. Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University &
2. Henan Cancer Hospital, Zhengzhou, Henan 450008, China
- Keywords:
Multiple myeloma;
Monocytes/macrophages;
Single-cell RNA sequencing;
Immune cell;
Microenvironment;
Bone marrow;
Molecular characterization
- From:
Chinese Medical Journal
2024;137(13):1603-1613
- CountryChina
- Language:Chinese
-
Abstract:
Background::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-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::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-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve 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 were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve 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, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::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.
