Department of Rheumatology, Ghent University Hospital, Ghent, Belgium; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
Department of Rheumatology, Ghent University Hospital, Ghent, Belgium; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium; Department of Haematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
Mol Immunol. 2018 Sep;101:521-526. doi: 10.1016/j.molimm.2018.08.019. Epub 2018 Aug 25.
Multiple myeloma (MM) is a progressive monoclonal B cell malignancy, for which survival and progression largely relies on the crosstalk of tumor cells with the bone marrow (BM) microenvironment, inducing immune escape, angiogenesis, bone destruction and drug resistance. Despite great therapeutic advances, most of the MM patients still relapse and remain incurable. Over the past years, immunotherapy has emerged as a new field in cancer therapy. Here, the immune cells of the patients themselves are activated to target the tumor cells. In MM, several effector cells of the immune system are present in the BM microenvironment; unfortunately, they are mostly all functionally impaired. In this review, we focus on the role of innate-like T cells in MM, particularly CD1d- and MR1- restricted T cells such as respectively invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells. These cells have the capacity upon activation to rapidly release copious amounts of cytokines affecting a wide range of innate and adaptive immune responses, and could therefore play a key protective role in anti-tumor immunity. We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM.
多发性骨髓瘤（MM）是一种进行性单克隆 B 细胞恶性肿瘤，其生存和进展在很大程度上依赖于肿瘤细胞与骨髓（BM）微环境的相互作用，从而诱导免疫逃逸、血管生成、骨质破坏和耐药性。尽管有了很大的治疗进展，但大多数 MM 患者仍会复发，且无法治愈。在过去的几年中，免疫疗法已成为癌症治疗的一个新领域。在这里，患者自身的免疫细胞被激活以靶向肿瘤细胞。在 MM 中，免疫系统的几种效应细胞存在于 BM 微环境中；不幸的是，它们大多都功能受损。在这篇综述中，我们重点关注固有样 T 细胞在 MM 中的作用，特别是 CD1d 和 MR1 限制性 T 细胞，如分别为不变自然杀伤 T（iNKT）细胞和黏膜相关不变 T（MAIT）细胞。这些细胞在激活后能够迅速释放大量细胞因子，影响广泛的先天和适应性免疫反应，因此在抗肿瘤免疫中可能发挥关键的保护作用。我们描述了 iNKT 和 MAIT 细胞在 MM 病理中的功能耗竭的最新观察结果，并讨论了检查点抑制作为延长这些免疫调节性 T 细胞激活的有吸引力的治疗 MM 的靶点的潜在应用。
