Th17.1细胞在抗BCMA CAR T细胞治疗多发性骨髓瘤后引起类肉芽肿炎症反应。
Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma.
发表日期:2023 Jan 31
作者:
Alexander M Leipold, Rudolf A Werner, Johannes Düll, Pius Jung, Mara John, Emilia Stanojkovska, Xiang Zhou, Hannah Hornburger, Anna Ruckdeschel, Oliver Dietrich, Fabian Imdahl, Tobias Krammer, Stefan Knop, Andreas Rosenwald, Andreas Buck, Leif Erik Sander, Hermann Einsele, K Martin Kortüm, Antoine-Emmanuel Saliba, Leo Rasche
来源:
LEUKEMIA
摘要:
伪进展和爆发现象是免疫肿瘤药物治疗后患者随访中的一种新的诊断挑战。我们提出了一个以Idecabtagen Vicleucel(Ide-cel)为例的肺爆发病例研究,该药物是针对BCMA的CAR T细胞疗法,并使用单细胞RNA测序(scRNA-seq)鉴定了一个Th17.1驱动的自身免疫机制作为这种现象的生物学基础。通过整合不同肺部病理情况的数据集,我们揭示了CAR T后肺部病变和结节病之间的转录组相似性。此外,我们探索了一种非侵入性PET诊断方法,并表明与CXCR4结合的示踪剂可以在这种情况下补充FDG PET成像,区分免疫介导的变化和CAR T细胞治疗后的真正复发。总而言之,我们的研究强调了一个Th17.1驱动的CAR T后自身免疫现象,可能被误解为疾病复发,并且多PET示踪剂成像和scRNA-seq诊断方法可以帮助解决这一诊断难题。©2023.作者(们)。
Pseudo-progression and flare-up phenomena constitute a novel diagnostic challenge in the follow-up of patients treated with immune-oncology drugs. We present a case study on pulmonary flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T-cell therapy, and used single-cell RNA-seq (scRNA-seq) to identify a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon. By integrating datasets of various lung pathological conditions, we revealed transcriptomic similarities between post CAR T pulmonary lesions and sarcoidosis. Furthermore, we explored a noninvasive PET based diagnostic approach and showed that tracers binding to CXCR4 complement FDG PET imaging in this setting, allowing discrimination between immune-mediated changes and true relapse after CAR T-cell treatment. In conclusion, our study highlights a Th17.1 driven autoimmune phenomenon after CAR T, which may be misinterpreted as disease relapse, and that imaging with multiple PET tracers and scRNA-seq could help in this diagnostic dilemma.© 2023. The Author(s).