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目的 探讨靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T）治疗前后多发性骨髓瘤（MM）肿瘤细胞的分子特征变化，分析不变链（CD74）表达改变及其与巨噬细胞迁移抑制因子（MIF）的潜在关联。方法 纳入BCMA CAR-T输注前及输注后≥3个月的骨髓配对样本，在恶性浆细胞相关群体中开展差异表达分析并进行功能富集和细胞通讯分析。以U266细胞系为模型进行共培养实验及MIF刺激实验，并采用CCK-8与EdU实验检测其细胞增殖能力。结果 治疗后3个月及以上的MM细胞出现CD74表达上调，且4对样本治疗后CD74表达均高于治疗前。治疗后整体上调基因主要涉及抗原加工与递呈、细胞黏附及免疫相关过程，且存在以MIF相关轴为代表的显著互作信号。体外实验显示，共培养条件下肿瘤细胞膜CD74增加，MIF刺激可促进U266细胞增殖。结论 BCMA CAR-T治疗后MM肿瘤相关细胞CD74表达上调，并伴随MIF/CD74激活，值得进一步深入研究其在治疗后适应性改变中的作用及潜在干预价值。
Abstract：Objective To 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).Methods Paired 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.Results CD74 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.Conclusion CD74 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.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.08.006
中图分类号:R733.3
引用信息:
[1]陈新卓,吴凡,王会平,等.MIF/CD74轴对多发性骨髓瘤BCMA CAR-T耐药的潜在作用研究[J].安徽医科大学学报,2026,61(08):1375-1382.DOI:10.19405/j.cnki.issn1000-1492.2026.08.006.
基金信息:
国家自然科学基金项目（编号：82200225、82370225）~~
2026-07-20
2026-07-20
2026-07-20