美国Dana-Farber癌症研究所Irene M. Ghobrial和美国哈佛医学院Gad Getz共同合作，近期取得重要工作进展。他们研究发现了高危阴燃性骨髓瘤患者对免疫治疗反应的免疫生物标志物。相关研究成果2022年11月14日在线发表于《癌细胞》杂志上。

研究人员在高危SMM患者中进行了埃洛妥珠单抗、来那度胺和地塞米松（EloLenDex）的II期试验，并对患者和健康供体（HD）的149份骨髓（BM）和外周血（PB）样本进行单细胞RNA和T细胞受体（TCR）测序。研究人员发现早期使用EloLenDex治疗是安全有效的，他们提供了患者免疫细胞组成和TCR谱多样性变化的综合表征。

患者的免疫细胞组成与HD的相似性可能在诊断和治疗后具有预后相关性，颗粒酶K（GZMK）⁺ CD8⁺效应记忆T（TEM）细胞的丰度可能与治疗反应相关。在BM和PB中观察到的免疫改变之间的相似性表明，基于PB的免疫分析可能具有诊断和预后的效用。

据介绍，阴燃性多发性骨髓瘤(SMM)患者在病情进一步严重后才能被观察到，但早期治疗可能会改善预后。

附：英文原文

Title: Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma

Author: Romanos Sklavenitis-Pistofidis, Michelle P. Aranha, Robert A. Redd, Joanna Baginska, Nicholas J. Haradhvala, Margaret Hallisey, Ankit K. Dutta, Alexandra Savell, Shohreh Varmeh, Daniel Heilpern-Mallory, Sylvia Ujwary, Oksana Zavidij, Francois Aguet, Nang K. Su, Elizabeth D. Lightbody, Mark Bustoros, Sabrin Tahri, Tarek H. Mouhieddine, Ting Wu, Lea Flechon, Shankara Anand, Jacalyn M. Rosenblatt, Jeffrey Zonder, James J. Vredenburgh, Adam Boruchov, Manisha Bhutani, Saad Z. Usmani, Jeffrey Matous, Andrew J. Yee, Andrzej Jakubowiak, Jacob Laubach, Salomon Manier, Omar Nadeem, Paul Richardson, Ashraf Z. Badros, Maria-Victoria Mateos, Lorenzo Trippa, Gad Getz, Irene M. Ghobrial

Issue&Volume: 2022/11/14

Abstract: Patients with smoldering multiple myeloma (SMM) are observed until progression, butearly treatment may improve outcomes. We conducted a phase II trial of elotuzumab,lenalidomide, and dexamethasone (EloLenDex) in patients with high-risk SMM and performedsingle-cell RNA and T cell receptor (TCR) sequencing on 149 bone marrow (BM) and peripheralblood (PB) samples from patients and healthy donors (HDs). We find that early treatmentwith EloLenDex is safe and effective and provide a comprehensive characterizationof alterations in immune cell composition and TCR repertoire diversity in patients.We show that the similarity of a patient’s immune cell composition to that of HDsmay have prognostic relevance at diagnosis and after treatment and that the abundanceof granzyme K (GZMK)+ CD8+ effector memory T (TEM) cells may be associated with treatment response. Last, we uncover similarities between immune alterations observed in the BM and PB, suggestingthat PB-based immune profiling may have diagnostic and prognostic utility.

DOI: 10.1016/j.ccell.2022.10.017

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00508-6