CD155/TIGIT signalling plays a vital role in the regulation of bone marrow mesenchymal stem cell–induced natural killer–cell exhaustion in multiple myeloma

作者：Zhaoyun Liu, Ling Deng, Yue Jia, Hui Liu, Kai Ding, Wei Wang, Hongkai Zhang, Rong Fu · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.861 · 被引用次数：20 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

Dear Editor, T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is a potential immune checkpoint for natural killer (NK)-cell exhaustion in multiple myeloma (MM), and its ligand, CD155 on bone marrow mesenchymal stem cells (BMSCs), is highly expressed in newly diagnosed MM (NDMM) but expressed at extremely low levels on myeloma cells. CD155/TIGIT signalling is involved in the regulation of BMSC-induced NK-cell exhaustion. MM is an incurable disease, and most patients eventually relapse or develop drug-resistant disease. BMSCs, an important cellular component of the bone marrow microenvironment, are critical for cell-based immunotherapy because they modulate the functions of several immune cell types. BMSCs promote myeloma cell malignant proliferation in various ways. Meanwhile, myeloma cells can also reprogram BMSCs, which promotes the formation of a malignant regulatory loop based on BMSC–myeloma cell interactions.1-4 NK cells are lymphocytes that kill tumour cells without prior sensitisation, because the expression of MHC class I is low on myeloma cells and they are easily recognised by NK cells at the early disease stage.5, 6 With disease progression, the expression of inhibitory immune checkpoints on NK cells is increased, leading to NK-cell exhaustion and tumour cell immune escape. TIGIT is expressed on lymphocytes with an inhibitory role.7 Its immunoglobulin domain is similar to the amino terminal domain of CD226, both of which can bind their ligands CD15...