CD71+ erythroid cells promote multiple myeloma progression and impair anti-bacterial immune response
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 immuno...
Saved in:
| Published in: | British journal of haematology |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
20-11-2024
|
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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.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. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1365-2141 1365-2141 |
| DOI: | 10.1111/bjh.19914 |