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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Single-cell and functional profiling identifies an IL6-centered immunometabolic communication circuit in multiple
Delong Lang1, Jing Wu2, Jiayou Zhang2
1Department of Hematology, Fuyang People's Hospital (The Affiliated Fuyang People's Hospital of Anhui Medical University), Fuyang, Anhui, China.
Frontiers in Immunology
|August 11, 2026
Summary
Multiple myeloma cells thrive in the bone marrow niche, driven by immune dysfunction and metabolic stress. Targeting linked IL-6, glycolytic, and glutamine pathways offers new therapeutic strategies for this cancer.
Area of Science:
- Immunology and Cancer Biology
- Metabolic Pathways in Cancer
- Bone Marrow Microenvironment
Background:
- Multiple myeloma (MM) is sustained by a complex bone marrow niche involving malignant plasma cells, immune cells, and metabolic dysregulation.
- Understanding the intricate interactions within this niche is crucial for developing effective MM therapies.
Purpose of the Study:
- To resolve the cellular and molecular ecosystem of the multiple myeloma bone marrow niche at a compartment-level resolution.
- To identify key immunometabolic pathways and cell-cell communication networks driving MM progression.
- To explore potential therapeutic vulnerabilities by targeting identified metabolic pathways.
Main Methods:
- Integrated analysis of single-cell RNA sequencing data from 95,940 bone marrow cells.
- Pathway scoring, cell-cell communication inference (CellChat), clinical validation, multiplex immunofluorescence, and metabolic perturbation experiments.
- In vitro testing of lactate dehydrogenase (LDH) and glutamine transporter inhibitors.
Main Results:
- Identified 32 distinct cell populations and significant microenvironmental remodeling in MM, including altered immune cell compartments and inflammatory programs.
- Revealed recurrent immunometabolic pathways (e.g., IL6-JAK-STAT3, mTORC1, oxidative phosphorylation) and rewiring of ligand-receptor networks.
- Demonstrated that inhibiting LDH and glutamine transport synergistically suppressed multiple myeloma cell viability in vitro.
Conclusions:
- Established an IL-6-centered immunometabolic communication circuit linking malignant plasma cells, tumor-associated macrophages (TAMs), and dysfunctional T cells in MM.
- Identified cooperative glycolytic/lactate and glutamine-dependent metabolic vulnerabilities as functional targets in multiple myeloma.
- These findings support novel therapeutic strategies targeting metabolic pathways in the multiple myeloma niche.
