Reduced HLA-I Transcript Levels and Increased Abundance of a CD56 dim NK Cell Signature Are Associated with Improved Survival in Lower-Grade Gliomas.
Simple Summary: Human leukocyte antigen class I (HLA-I) molecules can modulate anti-tumour immune responses from CD8+ T cells and NK cells. However, how deregulated HLA-I expression impacts clinical outcomes in cancer patients has remained unclear. Using computational approaches, we investigated the...
| Publicado en: | Cancers Vol. 17; no. 9; pp. 1570 - 1590 |
|---|---|
| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
MDPI
May2025
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=185133408&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 185133408 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: May2025 vid: 17 iid: 9 pid: 97109 pub: MDPI artinfo: ui: 185133408 185133408 185133408 10.3390/cancers17091570 185133408 ppf: 1570 ppct: 20 formats: tig: atl: Reduced HLA-I Transcript Levels and Increased Abundance of a CD56 dim NK Cell Signature Are Associated with Improved Survival in Lower-Grade Gliomas. aug: au: Khan, Md Abdullah Al Kamran Peel, Lorenza Sedgwick, Alexander J. Sun, Yuhan Vivian, Julian P. Corbett, Alexandra J. Dolcetti, Riccardo Mantamadiotis, Theo Barrow, Alexander D. affil: Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia sug: subj: Glioma Prognosis Histocompatibility Antigens Killer Cells, Natural Tumor Cells, Cultured HLA Antigens Outcome Assessment Human Gene Expression Profiling Methods Receptors, Cell Surface RNA Immunotherapy Overall Survival Funding Source ab: Simple Summary: Human leukocyte antigen class I (HLA-I) molecules can modulate anti-tumour immune responses from CD8+ T cells and NK cells. However, how deregulated HLA-I expression impacts clinical outcomes in cancer patients has remained unclear. Using computational approaches, we investigated the association of HLA-I molecules with patient survival by analysing gene expression datasets across multiple cancers. We observed a trend toward poor survival in patients with high HLA-I expression in lower-grade gliomas. Moreover, the favourable prognostic association of CD56dim NK cells was attenuated in the context of abundant HLA-I, as suggested by the correlation between NK cell receptors NKG2A/C/E and HLA-E. Overall, our study provides a computational framework that offers insights into HLA-I-mediated modulation of cytotoxic NK cell activity using cancer gene expression datasets, with potential applicability for other diseases. Background: Human leukocyte antigen class I (HLA-I) plays a pivotal role in shaping anti-tumour immunity by influencing the functionality of T cells and natural killer (NK) cells within the tumour microenvironment. Methods: Here, we explored the transcriptional landscape of HLA-I molecules across various solid cancer transcriptomes from The Cancer Genome Atlas (TCGA) database and assessed the impact of HLA-I expression on the clinical significance of tumour-infiltrating CD56dim and CD56bright NK cells. Results: Our analysis revealed that high HLA-I expression correlated with reduced patient survival in the TCGA lower-grade glioma (LGG) cohort, with this association varying by histopathological subtype. We then estimated the relative abundance of 23 immune and stromal cell signatures in LGG transcriptomes using a cellular deconvolution approach, which revealed that LGG patients with low HLA-I expression and high CD56dim NK cell abundance had better survival outcomes compared to those with high HLA-I expression and low CD56dim NK cell abundance. Furthermore, HLA-I expression was positively correlated with various inhibitory NK cell receptors and negatively correlated with activating NK cell receptors, particularly those within the killer cell lectin-like receptor (KLR) gene family. High co-expression of HLA-E and NKG2A predicted poor survival outcomes in LGG patients, whereas low HLA-E and high NKG2C/E abundance predicted more favourable outcomes, suggesting a potential modulatory role of HLA-I on the tumour-infiltrating cytotoxic CD56dim NK cell subset. Conclusions: Overall, our study unveils a potential role for deregulated HLA-I expression in modulating the clinical impact of glioma-infiltrating CD56dim NK cells. These findings lay the foundation for future in-depth experimental studies to investigate the underlying mechanisms. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|