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

Cheng, Yan; Sun, Fumou; Alapat, Daisy V.; Wanchai, Visanu; Mery, David; Guo, Wancheng; Cao, Huojun; Zhu, Yuqi; Ashby, Cody; Bauer, Michael Anton; Nookaew, Intawat; Siegel, Eric R.; Ying, Jun; Chen, Jin-Ran; Gai, Dongzheng; Peng, Bailu; Xu, Hongwei; Bailey, Clyde; Al Hadidi, Samer; Schinke, Carolina; Thanendrarajan, Sharmilan; Zangari, Maurizio; Chesi, Marta; Bergsagel, P. Leif; van Rhee, Frits; Janz, Siegfried; Tricot, Guido; Shaughnessy, John D.; Zhan, Fenghuang

doi:10.1016/j.xcrm.2023.101214

Cited by 6 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Initially, NEK2's promotion of the cell cycle was identified as a major factor contributing to its pro-tumor effects. As a result, the objective of targeting NEK2 to achieve effective anti-tumor outcomes is centered around inhibiting the progression of cancer cells through slowing down their cell cycle during mitosis and cytokinesis [29,30]. NEK2 is upregulated in cancer and has been linked to the initiation, advancement, spread, and resistance to treatment of tumors [31].…”

Section: Discussionmentioning

confidence: 99%

NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells

Zhang,

Yu,

et al. 2024

neo

View full text Add to dashboard Cite

The most common primary malignant tumor in the adult brain is glioblastoma multiforme (GBM); however, its underlying pathogenic mechanism remains elusive. The never in mitosis (NIMA)related kinase 2 (NEK2) has been closely associated with the prognosis of various malignancies.Nevertheless, the complete elucidation of NEK2's potential clinical value, particularly in glioma prognosis and development, remains lacking. U87MG and A172 glioblastoma cells were infected with sh-NEK2 lentivirus or oe-NEK2 plasmid to investigate the effect of NEK2 on cell proliferation, migration, and invasion. Cell viability was measured using CCK-8 and colony formation assays, while Transwell assay was utilized to assess cell migration and invasion. Protein expression levels were determined through western blot analysis. Additionally, CGGA and TCGA databases were used for bioinformatics analysis in order to examine the NEK2 expression. Through comprehensive bioinformatics analysis, we identified elevated mRNA expression levels of NEK2 in gliomas compared to normal tissues, which correlated with poor prognosis among glioma patients.Moreover, functional experiments revealed that silencing NEK2 suppressed glioma cell proliferation while overexpression of NEK2 promoted migration and invasion capabilities. Finally, our study uncovered that NEK2 regulates the malignant progression of TP53 wild-type glioblastoma by facilitating TP53 ubiquitination.

show abstract

Section: Discussionmentioning

confidence: 99%

NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells

Zhang,

Yu,

et al. 2024

neo

View full text Add to dashboard Cite

show abstract

“…As an IFN-γ induced product, tumor PD-L1 expression is regarded as an efficacy predictive biomarker for anti-PD-L1 treatment 48 . Moreover, the elevation of PD-L1 levels may be accompanied by a better therapeutic effect of PD-L1 antibody 49 . Our study found that INHBA might suppress tumor PD-L1 induced by IFN-γ, possibly from T cells, leading to the failure of PD-L1 blockade.…”

Section: Discussionmentioning

confidence: 99%

INHBA/Activin A promotes tumor growth and induces resistance to anti-PD-L1 therapy by suppressing IFN-γ signaling

Li,

Gu,

Tong

et al. 2023

Preprint

View full text Add to dashboard Cite

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, respectively, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. As evidenced by our RNA-Seq and in vitro results, the interferon-γ (IFN-γ) signaling pathway was significantly down-regulated by tumor intrinsic activin A. Tumor INHBA deficiency led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 therapy. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment. Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy. Our findings reveal that INHBA/activin A is involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway and considered to be a potential target to overcome anti-PD-L1 resistance in clinical cancer treatment.

show abstract

“…Extending on their work, in this issue of Cell Reports Medicine , Cheng et al. 1 demonstrate in a comprehensive study that environmental blocking of NEK2 delays MM tumor progression by enhancing anti-tumor immunity.…”

Section: Main Textmentioning

confidence: 93%

“…Initially, Cheng et al. 1 investigated the effect of NEK2 deletion in two different lymphoma models (Eμ-myc transgenic mice as an aggressive B cell lymphoma model and 5TGM1 as an immunocompetent MM model). In both disease models, loss of NEK2 resulted in reduced tumor burden and significantly prolonged survival.…”

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

Breaking barriers: NEK2 inhibition shines in multiple myeloma treatment

Lischer,

Bruns

2023

Cell Reports Medicine

View full text Add to dashboard Cite

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

Cited by 6 publications

References 58 publications

NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells

NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells

INHBA/Activin A promotes tumor growth and induces resistance to anti-PD-L1 therapy by suppressing IFN-γ signaling

Breaking barriers: NEK2 inhibition shines in multiple myeloma treatment

Contact Info

Product

Resources

About