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Updated: Feb 16, 2026

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
CD86 regulates myeloma cell survival
Catherine M Gavile1, Benjamin G Barwick1, Scott Newman2
1Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.
Abstract:
Although prognosis for patients with multiple myeloma has improved over the past decade, research toward discovery of new therapeutic avenues is important and could lead to a cure for this plasma cell malignancy. Here we show that blocking the CD28-CD86 pathway via silencing of either CD28 or CD86 leads to myeloma cell death. Inhibiting this pathway leads to downregulation of integrins and IRF4, a known myeloma survival factor. Our data also indicate that CD86, the canonical ligand in this pathway, has prosurvival activity that is dependent on its cytosolic domain. These findings indicate that targeting of this pathway is a promising therapeutic avenue for myeloma, because it leads to modulation of different processes important in cell viability.
Insights
Blocking the CD28-CD86 pathway induces death in multiple myeloma cells. This approach downregulates key survival factors, offering a promising new therapeutic strategy for this plasma cell malignancy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Multiple myeloma, a plasma cell malignancy, has seen improved prognoses but still requires novel therapeutic strategies for a potential cure.
- The CD28-CD86 co-stimulatory pathway plays a role in immune regulation and cell survival.
Purpose of the Study:
- To investigate the therapeutic potential of targeting the CD28-CD86 pathway in multiple myeloma.
- To elucidate the mechanisms by which this pathway influences myeloma cell viability.
Main Methods:
- Silencing of CD28 or CD86 genes in myeloma cells.
- Analysis of downstream effects on integrin and IRF4 expression.
- Assessment of cell death induction and survival factor modulation.
Main Results:
- Silencing CD28 or CD86 effectively induced myeloma cell death.
- Inhibition of the CD28-CD86 pathway led to downregulation of integrins and IRF4, a crucial myeloma survival factor.
- The prosurvival activity of CD86 was found to be dependent on its cytosolic domain.
Conclusions:
- Targeting the CD28-CD86 pathway represents a promising therapeutic strategy for multiple myeloma.
- Modulation of this pathway impacts critical cellular processes involved in myeloma cell viability, suggesting its potential as a novel treatment avenue.
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