文章：

质谱流式细胞术剖析常见异常蛋白血症在诊断时及一线治疗前后肿瘤免疫微环境中T细胞的异质性

Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies

原文发布日期：2019-08-28

DOI: 10.1038/s41408-019-0234-4

类型: Article

开放获取: 是

英文摘要：

Dysproteinemias progress through a series of clonal evolution events in the tumor cell along with the development of a progressively more “permissive” immune tumor microenvironment (iTME). Novel multiparametric cytometry approaches, such as cytometry by time-of-flight (CyTOF) combined with novel gating algorithms can rapidly characterize previously unknown phenotypes in the iTME of tumors and better capture its heterogeneity. Here, we used a 33-marker CyTOF panel to characterize the iTME of dysproteinemia patients (MGUS, multiple myeloma—MM, smoldering MM, and AL amyloidosis) at diagnosis and after standard of care first line therapies (triplet induction chemotherapy and autologous stem cell transplant—ASCT). We identify novel subsets, some of which are unique to the iTME and absent from matched peripheral blood samples, with potential roles in tumor immunosurveillance as well as tumor immune escape. We find that AL amyloidosis has a distinct iTME compared to other dysproteinemias with higher myeloid and “innate-like” T cell subset infiltration. We show that T cell immune senescence might be implicated in disease pathogenesis in patients with trisomies. Finally, we demonstrate that the early post-ASCT period is associated with an increase of senescent and exhausted subsets, which might have implications for the rational selection of post-ASCT therapies.
 

摘要翻译： 

异常蛋白血症的进展经历肿瘤细胞一系列克隆进化事件，同时伴随免疫肿瘤微环境逐渐变得更为“许可”。新型多参数流式细胞术方法，例如飞行时间流式细胞技术与新型门控算法相结合，能够快速表征肿瘤免疫微环境中先前未知的表型，并更好地捕捉其异质性。本研究采用33标志物CyTOF面板，对异常蛋白血症患者在诊断时及接受标准一线治疗后的免疫微环境进行表征。我们识别出新的细胞亚群，其中部分亚群为免疫微环境所特有，在匹配的外周血样本中缺失，这些亚群可能在肿瘤免疫监视及免疫逃逸中发挥作用。我们发现，与其他异常蛋白血症相比，AL淀粉样变性的免疫微环境具有独特性，表现为更高的髓系细胞和“先天样”T细胞亚群浸润。研究表明，在三体核型患者中，T细胞免疫衰老可能参与疾病发病机制。最后，我们证实ASCT术后早期阶段与衰老和耗竭亚群的增加相关，这可能对ASCT后治疗方案的合理选择具有指导意义。

原文链接：

Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies