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Updated: Feb 13, 2026
09:41
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
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Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression
Yawara Kawano1,2, Oksana Zavidij1, Jihye Park1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
The Journal of Clinical Investigation
|March 21, 2018
Summary
Myeloma cells expand regulatory T cells (Tregs) by secreting type 1 interferon (IFN). Blocking this IFN signaling pathway halts Treg expansion and combats multiple myeloma progression, offering a new therapeutic strategy.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- Multiple myeloma (MM) remains a significant challenge, with most patients experiencing disease progression despite treatment advances.
- Regulatory T cells (Tregs) are implicated in MM progression due to their immunosuppressive functions.
Purpose of the Study:
- To investigate the role of type 1 interferon (IFN) in myeloma-driven Treg expansion and activation.
- To evaluate the therapeutic potential of blocking IFN signaling in MM.
Main Methods:
- Utilized syngeneic murine myeloma models and human bone marrow aspirates.
- Analyzed Treg expansion and activation in the bone marrow microenvironment.
- Employed gene sequencing and enrichment analysis to uncover cellular interactions.
- Tested the efficacy of IFN α and β receptor 1 (IFNAR1) blockade via antibodies and genetic knockout.
Main Results:
- Myeloma cells were found to secrete type 1 IFN, driving Treg expansion and activation.
- Blocking IFNAR1 significantly reduced Treg immunosuppressive function and myeloma progression in mouse models.
- Selective Treg depletion resulted in complete remission and prolonged survival in mice.
- IFNAR1 blockade led to decreased Treg proliferation and improved survival in myeloma-injected mice.
Conclusions:
- Type 1 IFN signaling is a key mechanism by which myeloma cells promote Treg expansion.
- Targeting type 1 IFN signaling represents a promising therapeutic strategy to overcome Treg-mediated immunosuppression in multiple myeloma.
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