Data from Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy

• DOI: 10.1158/1078-0432.c.7447774.v1
• Publication Date: 2024-09-13T08:31:45Z
• Authors: Yazi Yang; Sen Qin; Mengyu Yang; Ting Wang; Ru Feng; Chunli Zhang; Enrun Zheng; Qinghua Li; Pengyu Xiang; Shangyong Ning; Xiaodong Xu; Xin Zuo; Shuai Zhang; Xiaoya Yun; Xuehong Zhou; Yue Wang; Lin He; Yongfeng Shang; Luyang Sun; Hui Liu
• Keywords: CAR T-cell therapy

<div>AbstractPurpose:<p>The purpose of this study was to investigate the remodeling multiple myeloma microenvironment after B-cell maturation antigen (BCMA)–targeted chimeric receptor T (CAR-T) cell therapy.</p>Experimental Design:<p>We performed single-cell RNA sequencing on paired bone marrow specimens (<i>n</i> = 14) from seven patients with before (i.e., baseline, “day −4”) and 28”) lymphodepleted BCMA CAR-T therapy.</p>Results:<p>Our analysis revealed heterogeneity in gene expression profiles among cells, even those harboring same cytogenetic abnormalities. The best overall responses over 15-month follow-up are positively correlated abundance targeted cytotoxic activity CD8<sup>+</sup> effector cells day 28 infusion. Additionally, favorable associated attenuated immunosuppression mediated by regulatory enhanced T-cell activity, elevated type 1 conventional dendritic (DC) presentation ability. DC re-clustering inferred intramedullary-originated 3 DCs extramedullary migration. Cell–cell communication network indicated that therapy mitigates BAFF/GALECTIN/MK pathway–mediated activates MIF anti–multiple immunity.</p>Conclusions:<p>Our sheds light dynamics therapy, offering clues for predicting treatment responsivity.</p></div>