Journal article
High NEK2 expression in myeloid progenitors suppresses T cell immunity in multiple myeloma
Cell reports. Medicine, Vol.4(10), 101214
10/2023
DOI: 10.1016/j.xcrm.2023.101214
PMCID: PMC10591052
PMID: 37794587
Abstract
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.
Details
- Title: Subtitle
- High NEK2 expression in myeloid progenitors suppresses T cell immunity in multiple myeloma
- Creators
- Yan Cheng - Winthrop Rockefeller FoundationFumou Sun - Winthrop Rockefeller FoundationDaisy V. Alapat - University of Arkansas for Medical SciencesVisanu Wanchai - University of Arkansas for Medical SciencesDavid Mery - Winthrop Rockefeller FoundationWancheng Guo - Winthrop Rockefeller FoundationHuojun Cao - University of IowaYuqi Zhu - University of IowaCody Ashby - University of Arkansas for Medical SciencesMichael Anton Bauer - University of Arkansas for Medical SciencesIntawat Nookaew - University of Arkansas for Medical SciencesEric R. Siegel - University of Arkansas for Medical SciencesJun YingJin-Ran ChenDongzheng Gai - University of Arkansas for Medical SciencesBailu Peng - University of Arkansas for Medical SciencesHongwei XuClyde Bailey - Winthrop Rockefeller FoundationSamer Al Hadidi - University of Arkansas for Medical SciencesCarolina Schinke - Winthrop Rockefeller FoundationSharmilan Thanendrarajan - Winthrop Rockefeller FoundationMaurizio Zangari - Winthrop Rockefeller FoundationMarta Chesi - Mayo Clinic in ArizonaP. Leif Bergsagel - Mayo ClinicFrits van Rhee - University of Arkansas for Medical SciencesSiegfried Janz - Medical College of WisconsinGuido Tricot - Winthrop Rockefeller FoundationJohn D. Shaughnessy - University of Arkansas for Medical SciencesFenghuang Zhan - Winthrop Rockefeller Foundation
- Resource Type
- Journal article
- Publication Details
- Cell reports. Medicine, Vol.4(10), 101214
- DOI
- 10.1016/j.xcrm.2023.101214
- PMID
- 37794587
- PMCID
- PMC10591052
- NLM abbreviation
- Cell Rep Med
- ISSN
- 2666-3791
- eISSN
- 2666-3791
- Language
- English
- Electronic publication date
- 10/2023
- Date published
- 10/2023
- Academic Unit
- Anatomy and Cell Biology; Endodontics; Pathology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984473764302771
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