Changes in immune cell populations following KappaMab, lenalidomide and low-dose dexamethasone treatment in multiple myeloma

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2023-11-30 DOI:10.1002/cti2.1478

Samuel E Norton, Tiffany Khong, Malarmathy Ramachandran, Andrew J Highton, Kirsten A Ward-Hartstonge, Jake Shortt, Andrew Spencer, Roslyn A Kemp

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Abstract

Objectives

Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows in vitro synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa-restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM via multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation in vitro. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low-dose DEX in kappa-restricted relapsed/refractory MM ex vivo and assessed association of those changes with patient outcome.

Methods

A cohort (n = 40) of patients with kappa-restricted relapsed/refractory MM, treated with KM, LEN and low-dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment.

Results

We found changes in five DC and 17 T-cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector-memory CD4 T cells and effector CD8 T cells, indicating an activated immune response.

Conclusion

These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms via immune cells.

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卡帕单抗、来那度胺和低剂量地塞米松治疗多发性骨髓瘤后免疫细胞群的变化

来那度胺(Lenalidomide, LEN)用于治疗多发性骨髓瘤(MM)，并与KappaMab (KM)显示出体外协同作用，KappaMab是Kappa骨髓瘤抗原特异性的嵌合抗体，Kappa骨髓瘤抗原仅在Kappa限制性MM细胞表面表达。来那度胺、地塞米松(DEX)和KM通过多种免疫调节机制控制MM;然而，药物组合对免疫细胞有一些额外的影响。来那度胺可增加体外T细胞和NKT细胞的细胞毒性和树突状细胞(DC)的活化。我们研究了在体外接受KM、LEN和低剂量DEX治疗的kappa限制性复发/难治性MM患者的骨髓免疫细胞群，并评估了这些变化与患者预后的关系。方法:一组(n = 40) kappa限制性复发/难治性MM患者，接受KM、LEN和低剂量DEX治疗，使用可识别免疫细胞亚群的大规模细胞计数仪进行分析。聚类分析用于确定治疗后免疫细胞群在不同时间段的显著变化。结果:在整个治疗过程中，我们发现了5个DC和17个t细胞群的变化。我们发现激活的常规DC种群增加，未成熟/前体DC种群减少，激活的CD4 T细胞减少，效应记忆CD4 T细胞和效应CD8 T细胞增加，表明激活的免疫应答。结论:这些数据表征了LEN、DEX和KM治疗对MM非靶免疫细胞的影响。治疗可能通过直接作用和间接机制通过免疫细胞支持MM细胞的破坏。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.