Reduced HLA-I Transcript Levels and Increased Abundance of a CD56dim NK Cell Signature Are Associated with Improved Survival in Lower-Grade Gliomas

Khan, MAAK; Peel, L; Sedgwick, AJ; Sun, Y; Vivian, JP; Corbett, AJ; Dolcetti, R; Mantamadiotis, T; Barrow, AD

Author(s): Khan, MAAK; Peel, L; Sedgwick, AJ; Sun, Y; Vivian, JP; Corbett, AJ; Dolcetti, R; Mantamadiotis, T; Barrow, AD;
Details: Publication Year 2025-05-05,Volume 17,Issue #9,Page 1570
Journal Title: Cancers
Publication Type: Research article
Abstract: 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 CD56(dim) and CD56(bright) 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 CD56(dim) NK cell abundance had better survival outcomes compared to those with high HLA-I expression and low CD56(dim) 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 CD56(dim) NK cell subset. CONCLUSIONS: Overall, our study unveils a potential role for deregulated HLA-I expression in modulating the clinical impact of glioma-infiltrating CD56(dim) NK cells. These findings lay the foundation for future in-depth experimental studies to investigate the underlying mechanisms.
Publisher: MDPI
Keywords: CD56dim NK; Hla-i; NK cells; anti-tumour immunity; deconvolution; lower-grade glioma; prognosis; transcriptional signature
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.3390/cancers17091570
Open Access at Publisher's Site: https://doi.org/10.3390/cancers17091570
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-06-02 04:28:19

Last Modified: 2025-06-02 04:28:43