High NEK2 expression in myeloid progenitors suppresses T cell immunity in multiple myeloma

Cell Rep Med. 2023 Oct 17;4(10):101214. doi: 10.1016/j.xcrm.2023.101214. Epub 2023 Oct 3.


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-γ 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.

Keywords: NEK2; PD-L1; T cell immunity; bone marrow microenvironment; combination therapy; immune checkpoint blockade; interferon gamma gene signature; multiple myeloma; myeloid-derived suppressive cells; tumor-associated macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / genetics
  • Cell Line, Tumor
  • Mice
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / metabolism
  • Myeloid Progenitor Cells / metabolism
  • Myeloid Progenitor Cells / pathology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment


  • B7-H1 Antigen