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 CD56dimand CD56brightNK 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 CD56dimNK cell abundance had better survival outcomes compared to those with high HLA-I expression and low CD56dimNK 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 ofHLA-EandNKG2Apredicted poor survival outcomes in LGG patients, whereas lowHLA-Eand highNKG2C/Eabundance predicted more favourable outcomes, suggesting a potential modulatory role of HLA-I on the tumour-infiltrating cytotoxic CD56dimNK cell subset. Conclusions: Overall, our study unveils a potential role for deregulated HLA-I expression in modulating the clinical impact of glioma-infiltrating CD56dimNK cells. These findings lay the foundation for future in-depth experimental studies to investigate the underlying mechanisms.
背景：人类白细胞抗原I类（HLA-I）通过影响肿瘤微环境中T细胞和自然杀伤（NK）细胞的功能，在塑造抗肿瘤免疫中发挥关键作用。方法：本研究基于癌症基因组图谱（TCGA）数据库，系统分析了多种实体瘤转录组中HLA-I分子的表达谱，并评估了HLA-I表达对肿瘤浸润性CD56dim和CD56bright NK细胞临床意义的影响。结果：分析显示，在TCGA低级别胶质瘤（LGG）队列中，高HLA-I表达与患者生存率降低相关，且这种关联性因组织病理学亚型而异。通过细胞反卷积算法估算LGG转录组中23种免疫与基质细胞特征的相对丰度，发现与高HLA-I表达伴低CD56dim NK细胞丰度的患者相比，低HLA-I表达伴高CD56dim NK细胞丰度的LGG患者生存预后更佳。进一步分析表明，HLA-I表达与多种抑制性NK细胞受体呈正相关，而与激活型NK细胞受体（特别是杀伤细胞凝集素样受体（KLR）基因家族成员）呈负相关。HLA-E与NKG2A的高共表达预示LGG患者不良预后，而低HLA-E表达伴高NKG2C/E丰度则对应更有利的临床结局，提示HLA-I可能对肿瘤浸润性细胞毒性CD56dim NK细胞亚群具有调控作用。结论：本研究揭示了HLA-I表达失调在调节胶质瘤浸润性CD56dim NK细胞临床效应中的潜在作用，为后续深入探索其作用机制的实验研究奠定了基础。
肿瘤(癌症)患者之家