miR-34a promotes the immunosuppressive function of multiple myeloma-associated macrophages by dampening the TLR-9 signaling.
Cancer Med
; 13(11): e7387, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38864479
ABSTRACT
BACKGROUND:
Promising outcomes have been observed in multiple myeloma (MM) with the use of immunotherapies, specifically chimeric antigen receptor T (CAR-T) cell therapy. However, a portion of MM patients do not respond to CAR-T therapy, and the reasons for this lack of response remain unclear. The objective of this study was to investigate the impact of miR-34a on the immunosuppressive polarization of macrophages obtained from MM patients.METHODS:
The levels of miR-34a and TLR9 (Toll-like receptor 9) were examined in macrophages obtained from both healthy individuals and patients with MM. ELISA was employed to investigate the cytokine profiles of the macrophage samples. Co-culture experiments were conducted to evaluate the immunomodulatory impact of MM-associated macrophages on CAR-T cells.RESULTS:
There was an observed suppressed activation of macrophages and CD4+ T lymphocytes in the blood samples of MM patients. Overexpression of miR-34a in MM-associated macrophages dampened the TLR9 expression and impaired the inflammatory polarization. In both the co-culture system and an animal model, MM-associated macrophages suppressed the activity and tumoricidal effect of CAR-T cells in a miR-34a-dependent manner.CONCLUSION:
The findings imply that targeting the macrophage miR-34a/TLR9 axis could potentially alleviate the immunosuppression associated with CAR-T therapy in MM patients.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
MicroARNs
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Receptor Toll-Like 9
/
Mieloma Múltiple
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cancer Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
China