编者按：近年来，关于骨髓瘤进展的机制研究非常热门，研究的焦点集中在基因组学的改变上。然而，越来越多的证据表明，肿瘤细胞对于肿瘤微环境的改变足以影响骨髓瘤的发生与发展。在2014年美国血液学会（ASH）年会有关“骨髓瘤微环境及其免疫生物学”的科学研讨会上，美国耶鲁大学医学院血液科主任Madhav V. Dhodapkar教授详细介绍了免疫微环境如何影响免疫细胞，从而促发或抑制肿瘤细胞的生长及进化的过程，以及通过对相关机制的干预如何实现骨髓瘤的预防或治疗。会后，《肿瘤瞭望》就免疫微环境在骨髓瘤中的作用及影响对Dhodapkar教授进行了专访。

　　《肿瘤瞭望》：骨髓瘤中肿瘤细胞参与的免疫应答机制？

 

　　Prof.  Dhodapkar: We are beginning to appreciate that tumor cells engage several mechanisms to suppress the immune system. They make cytokines. They express molecules that shut off T-cells， for example. In addition， they are able to evade the immune system by expressing molecules that prevent T-cells， for example， getting into the tumor. One of the major new stories at this ASH meeting is the findings about the checkpoint blockade inhibitor class of drugs. They seem to be very active in certain hematologic malignancies and studies like this are going to allow us to overcome some of the immune suppressive effects that occur with tumor cells.

　　Dhodapkar 教授：肿瘤细胞有多种机制参与机体的免疫抑制，例如，它可以通过分泌一些细胞因子直接攻击T细胞；还能通过分泌一些因子，阻止T细胞进入肿瘤组织，从而实现免疫逃逸。今年ASH年会的主要亮点之一就是发现了检查点阻断（checkpoint blockade）抑制类药物，并证实在一些恶性血液病中似乎很有效。这方面的研究也表明我们能够克服肿瘤细胞对免疫抑制影响。

 

　　《肿瘤瞭望》： 2014 ASH年会上骨髓瘤方面的亮点？

 

　　Prof. Dhodapkar: In myeloma， there are several new advances. The most significant in the clinical setting has been the data presented from ASPIRE showing improvement in survival with kyprolis and its combinations. There are several new monoclonal antibodies entering the clinic. The two major antibodies in that regard are daratumumab and the SAR compound. There are also promising data from immune checkpoint blockade inhibitors and along with that， confirmation of data from older drugs with more follow-up like pomalidomide and elotuzumab showing these drugs are in fact improving survival in our patients. We have been blessed in the field of myeloma in having multiple new therapies to offer our patients as well as several new therapies in the pipeline.

　　Dhodapkar教授：在骨髓瘤领域中，的确有一些值得关注的新进展。在临床研究方面，最重要的成果来自于ASPIRE研究的数据，它表明kyprolis（卡非佐米，是一种蛋白酶体抑制剂类抗肿瘤药物，适用为治疗多发性骨髓瘤患者）以及其联合治疗方案在骨髓瘤患者的生存率方面的有显著改善。另外，还有几种新的单克隆抗体药物已应用于临床，其中两种主要药物为daratumumab和SAR化合物（均为anti-CD38单 抗）。与此同时，之前提到的免疫检查点阻断抑制剂的研究也取得了很大进展，例如pomalidomide（一种免疫调节剂，可以调节T细胞并抑制其增殖） 和elotuzumab（anti-CS1单抗）的研究表明有助于提高骨髓瘤患者的生存。我们对于骨髓瘤领域取得的进展感到非常欣慰，也期待未来有更多新的方案涌现出来。

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