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。

美国耶鲁大学医学院血液科主任Madhav V. Dhodapkar教授

 

　　《肿瘤瞭望》：在骨髓瘤发生发展过程中机体微环境变化的机制？

 

　　Prof. Dhodapkar: It is increasingly appreciated in myeloma that a major change in the disease involves changes in the microenvironment of the tumor. Although we have studied for a long time the genetic changes that occur in tumor cells， there are a lot of changes that occur in the microenvironment of normal cells. That includes changes in bone cells， in immune cells， changes in new blood vessels and so on. We think all of these things together play a very important role in how myeloma develops. It has become an important area of research because these are cells that can be easily targeted and can lead to improvements in outcomes. We have made substantial strides in myeloma in the context of improving outcomes but we have a long way to go to achieve sustained cures in the majority of patients.

　　Dhodapkar 教授：众多研究表明，骨髓瘤的主要特征在于其免疫微环境的改变。虽然我们对于骨髓瘤在基因组学上的研究了有很长一段时间，但是应该了解的是，正常细胞的微环境也发生了变化，其中包括骨细胞、免疫细胞、新生血管的变化等。我们认为，所有这些基因上的变异以及免疫微环境的改变共同导致了骨髓瘤的发生与发展。由于这些细胞比较容易靶向，因此已成为一个重要的研究领域，并且可能为改善骨髓瘤的临床治疗提供新的方向。

 

　　《肿瘤瞭望》：目前针对骨髓瘤微环境的变化有哪些最新的治疗方案?

 

　　Prof.  Dhodapkar: The one therapy that targets the microenvironment that is already in the clinic are the class of drugs that work on the bone such as bisphosphonates which are routinely used to treat myeloma and primarily work on the osteoclasts. What is in the pipeline and is already evident from many presentations at this meeting is that there are several approaches to try and manipulate the immune system and to overcome the suppression of the immune system that occurs with tumor cells. Those strategies are coming into the clinic and we expect over the next couple of years to see significant strides in that direction.

　　Dhodapkar教授：目前，针对骨髓瘤微环境改变有一类药物--双磷酸盐，已被用于骨髓瘤治疗，它主要作用于破骨细胞。在本届ASH年会上，有很多研究指出可通过多种途径调节肿瘤患者的免疫系统，来克服肿瘤细胞对人体免疫系统的抑制，这些方案即将进入临床。在接下来的几年中，我们期待着骨髓瘤治疗方案上有质的飞跃。

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