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Updated: Jun 7, 2025
In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
CD71+ erythroid cells promote multiple myeloma progression and impair anti-bacterial immune response
K Czubak1, T M Grzywa1,2, K Sidor-Dzitkowska3
1Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland.
Abstract:
Multiple myeloma (MM), one of the most frequent haematological malignancies, significantly increases the risk of bacterial infections due to treatment-related side effects, comorbidities and cancer-induced immune deficiencies. Recently, CD71+ erythroid cells (CECs) have been identified as key immunomodulators in neonates and cancer patients, but their role in MM progression remains unclear. Using a murine MM model, closely resembling human disease, we observed that MM progression is associated with anaemia and an increase in immature CECs, which are characterized by elevated arginase 2 (ARG2) expression. These MM-associated CECs suppress T-cell proliferation, contributing to impaired immune responses. Notably, ARG2 deficiency in mice led to slower MM progression and improved survival. Furthermore, MM-bearing mice exhibited higher susceptibility to Listeria monocytogenes infections, mirroring the increased infection risk in MM patients. Our findings suggest that ARG2-expressing CECs play a critical role in MM-associated immune suppression and infection susceptibility, pointing out ARG2 as a potential therapeutic target to enhance immune function and reduce infection risks in MM patients.
Insights
Multiple myeloma increases infection risk. Arginase 2-expressing CD71+ erythroid cells (CECs) suppress immune responses in this cancer, suggesting ARG2 as a therapeutic target.
Area of Science:
- Hematology
- Immunology
- Cancer Biology
Background:
- Multiple myeloma (MM) is a common blood cancer that weakens the immune system, increasing infection risk.
- CD71+ erythroid cells (CECs) are known immunomodulators, but their role in MM is not well understood.
Purpose of the Study:
- To investigate the role of CECs and arginase 2 (ARG2) in multiple myeloma progression and immune suppression.
- To explore ARG2 as a potential therapeutic target for MM-associated infections.
Main Methods:
- Utilized a murine model of multiple myeloma that mimics human disease.
- Analyzed the impact of ARG2 expression in CECs on T-cell proliferation and host susceptibility to Listeria monocytogenes infection.
Main Results:
- MM progression correlated with anemia and increased immature CECs expressing ARG2.
- These MM-associated CECs suppressed T-cell proliferation, impairing immune responses.
- Mice lacking ARG2 showed slower MM progression and improved survival.
- MM-bearing mice had increased susceptibility to bacterial infections.
Conclusions:
- ARG2-expressing CECs contribute significantly to immune suppression and infection susceptibility in multiple myeloma.
- Targeting ARG2 may offer a strategy to enhance immune function and reduce infection risk in MM patients.
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