Potential role of the MIF/CD74 axis in BCMA CAR-T resistance in multiple myeloma
10.19405/j.cnki.issn1000-1492.2026.08.006
- VernacularTitle:MIF/CD74轴对多发性骨髓瘤BCMA CAR-T耐药的潜在作用研究
- Author:
Xinzhuo CHEN
1
;
Fan WU
2
;
Huiping WANG
1
;
Zhimin ZHAI
1
;
Zhitao WANG
1
Author Information
1. The Second School of Clinical Medicine， Anhui Medical University， Hefei 230601
2. Department of Hematology， The Second Affiliated Hospital of Anhui Medical University， Hefei 230601
- Publication Type:Journal Article
- Keywords:
multiple myeloma;
BCMA CAR-T;
invariant chain;
macrophage migration inhibitory factor;
MIF;
CD74
- From:
Acta Universitatis Medicinalis Anhui
2026;61(8):1375-1382
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate molecular alterations in tumor cells of multiple myeloma （MM） before and after B-cell maturation antigen （BCMA）-directed chimeric antigen receptor T-cell （CAR-T） therapy， with a focus on changes in invariant chain （CD74） expression and its potential association with macrophage migration inhibitory factor （MIF）. MethodsPaired bone marrow samples collected before BCMA CAR-T infusion and at ≥3 months after infusion were analyzed. Differential gene expression， functional enrichment， and cell-cell communication analyses were performed in malignant plasma cell-related populations. In vitro coculture experiments and MIF stimulation assays were conducted using the U266 cell line， and cell proliferation was assessed by CCK-8 and EdU incorporation assays. ResultsCD74 expression was upregulated in MM cells at ≥3 months after BCMA CAR-T therapy， and CD74 expression was consistently higher in post-treatment samples than in paired pre-treatment samples across all four cases. Genes upregulated after treatment were mainly enriched in antigen processing and presentation， cell adhesion， and immune-related processes. Cell-cell communication analysis revealed prominent interaction signals involving MIF-related pathways. In vitro experiments showed that coculture conditions induced changes in membrane CD74 expression in tumor cells， and MIF stimulation promoted proliferation of U266 cells. ConclusionCD74 expression is upregulated in tumor-associated MM cells following BCMA CAR-T therapy and is accompanied by the activation of the MIF-CD74 axis， suggesting a potential role in post-treatment adaptive changes and warranting further investigation into its therapeutic relevance.
