CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies.
CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies.
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在多发性骨髓瘤（MM）中，抗CD38单克隆抗体Daratumumab已成为治疗武器库中不可或缺的药物，尽管临床研究中很少发现对Daratumumab反应的预测因素。
我们前瞻性收集了2016年至2020年间在我们中心接受一线或复发时Daratumumab治疗的97例患者的生物学数据。这些数据包括Daratumumab治疗前肿瘤浆细胞的多参数流式细胞术表型（CD200、CD117、CD56、CD38、CD45和CD27）、细胞遗传学和转录组基因表达谱（GEP）。
我们首先寻找对Daratumumab反应的预测因素。我们发现高CD56表达和CD45表达与更好的无进展生存期（PFS）显著相关，而高CD200表达与较差的PFS显著相关。然后，我们表明CD200-CD200R免疫突触通过改变NK细胞活性导致Daratumumab反应降低。
最后，我们证明抑制CD200可增加MM患者样本中对Daratumumab的反应，突显其作为Daratumumab反应预测生物标志物以及与Daratumumab联合治疗的可能治疗靶点的潜力。
本研究首次确定了肿瘤浆细胞表型和分子因素对Daratumumab反应的预测作用。肿瘤浆细胞上的CD200表达与较差的PFS相关。CD200-CD200R轴通过改变NK细胞活性导致抗CD38反应降低。
In multiple myeloma (MM), the anti-CD38 monoclonal antibody Daratumumab has become essential in the therapeutic arsenal, although very few predictive factors of response to Daratumumab have been identified in clinical studies.
We have prospectively collected biological data from 97 patients treated with Daratumumab in first line or at relapse in our center between 2016 and 2020. These data included multiparameter flow cytometry phenotype (CD200, CD117, CD56, CD38, CD45, and CD27), cytogenetic, and transcriptomic gene expression profiling (GEP) of tumor plasma cells before treatment with Daratumumab.
We first looked for predictive factors of response to Daratumumab.
We found that high CD56 expression and CD45 expression were significantly associated with better progression free survival (PFS) whereas high CD200 expression was significantly associated with poorer PFS. Then, we showed that the CD200-CD200R immune synapse is responsible for a decrease in Daratumumab response through the alteration of NK cells' activity.
Finally, we demonstrated that inhibition of CD200 increase response to Daratumumab in MM patient samples, highlighting its potential as a predictive biomarker for Daratumumab response and as a possible therapeutic target in combination with Daratumumab.
This study is the first to identify phenotypic and molecular factors' predictor of response to Daratumumab. CD200 expression on tumor plasma cell is associated with poorer progression free survival. CD200-CD200R axis is responsible for a decrease in anti-CD38 response through the alteration of NK cell activity.
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