In March 2023, a study led by Professor Rong Fu from Tianjin Medical University General Hospital was published in the prestigious international academic journal —— Clinical And Translational Medicine(IF=10.6). The title of the study is "Bone marrow-derived mesenchymal stem cells inhibit NK cell function via Tim-3/galectin-9 in multiple myeloma patients". The study delves into the complex interactions within the bone marrow microenvironment of multiple myeloma (MM) patients, focusing on how bone marrow mesenchymal stem cells (BMSCs) influence natural killer (NK) cell function.
MM is a hematological neoplasia characterized by the clonal proliferation of aberrant plasma cells, leading to significant health complications. Understanding the mechanisms by which BMSCs contribute to NK cell exhaustion, especially through the Tim-3/galectin-9 pathway, is crucial for developing novel therapeutic strategies to combat MM.
This research aims to elucidate the mechanism by which BMSCs from MM patients impact NK cell function, with a focus on the Tim-3/galectin-9 pathway. The study involved analyzing clinical samples from newly diagnosed MM patients and healthy donors to assess NK cell status. Additionally, single-cell RNA sequencing datasets were reanalyzed to evaluate gene expression in NK cells and BMSCs. The study also employed flow cytometry to detect Tim-3 ligands on BMSCs and MM cell lines, and established in vitro co-culture systems to study BMSC-NK cell interactions, both directly and indirectly.
（Clin Transl Med. 2023 Mar;13(3):e1224. ）
The study revealed that NK cells in MM patients exhibit an increased quantity but a decreased function. Notably, there was a higher expression of the HAVCR2 gene (Tim-3) in NK cells and LGALS9 (galectin-9) in BMSCs from MM patients. The research showed a negative correlation between Tim-3 expression and NK cell functionality, and the expression of galectin-9 on BMSCs correlated with the MM burden. BMSCs were found to inhibit NK cell function through the Tim-3/galectin-9 pathway, and this inhibition was observed both in direct cell-to-cell contact and indirectly through exosomes. Importantly, the study confirmed that blocking Tim-3 or galectin-9 could restore NK cell function.
（Clin Transl Med. 2023 Mar;13(3):e1224. ）
This research provides significant insights into the role of BMSCs in modulating NK cell function in the MM microenvironment, highlighting the Tim-3/galectin-9 pathway as a key mediator of NK cell exhaustion. These findings open up new possibilities for therapeutic intervention in MM. Targeting the Tim-3/galectin-9 interaction offers a promising approach to enhance the immune response against MM cells, potentially leading to more effective treatments for this challenging malignancy. The study’s identification of a critical pathway for NK cell dysfunction underscores the potential of targeted therapies in improving outcomes for MM patients.
