| First Author | Cheng Y | Year | 2023 |
| Journal | Cell Rep Med | Volume | 4 |
| Issue | 10 | Pages | 101214 |
| PubMed ID | 37794587 | Mgi Jnum | J:358115 |
| Mgi Id | MGI:7778540 | Doi | 10.1016/j.xcrm.2023.101214 |
| Citation | Cheng Y, et al. (2023) High NEK2 expression in myeloid progenitors suppresses T cell immunity in multiple myeloma. Cell Rep Med 4(10):101214 |
| abstractText | Multiple myeloma (MM) growth is supported by an immune-tolerant bone marrow microenvironment. Here, we find that loss of Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) in tumor microenvironmental cells is associated with MM growth suppression. The absence of NEK2 leads to both fewer tumor-associated macrophages (TAMs) and inhibitory T cells. NEK2 expression in myeloid progenitor cells promotes the generation of functional TAMs when stimulated with MM conditional medium. Clinically, high NEK2 expression in MM cells is associated with increased CD8(+) T effector memory cells, while low NEK2 is associated with an IFN-gamma gene signature and activated T cell response. Inhibition of NEK2 upregulates PD-L1 expression in MM cells and myeloid cells. In a mouse model, the combination of NEK2 inhibitor INH154 with PD-L1 blockade effectively eliminates MM cells and prolongs survival. Our results provide strong evidence that NEK2 inhibition may overcome tumor immune escape and support its further clinical development. |
