HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation

Hrbáč, Tomáš; Kopková, Alena; Siegl, František; Večeřa, Marek; Ruckova, Michaela; Kazda, Tomáš; Jančálek, Radim; Hendrych, Michal; Hermanová, Markéta; Vybíhal, Václav; Fadrus, Pavel; Smrčka, Martin; Sokol, Filip; Kubeš, Václav; Lipina, Radim; Slabý, Ondřej; Křen, Leoš; Šána, Jiří

doi:10.21873/cgp.20311

Cited by 12 publications

(11 citation statements)

References 87 publications

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“…HLA‐F interaction with inhibitory and activator receptors expressed by immune effector cells remains to be fully understood as its main interacting receptor KIR3DS1 is absent from some individuals 9–13 . Besides, data support its implication in tissue proliferation, 24 and exemplified in glioblastoma progression 45,46 . Therefore, influence of HLA‐F polymorphisms on its expression, along with the low HLA‐F expression in women suffering from unsuccessful treatment in pregnancy outcome, 34,35,47 supports an implication of this molecule in cell proliferation process.…”

Section: Discussionmentioning

confidence: 90%

“…[9][10][11][12][13] Besides, data support its implication in tissue proliferation, 24 and exemplified in glioblastoma progression. 45,46 Therefore, influence of HLA-F polymorphisms on its expression, along with the low HLA-F expression in women suffering from unsuccessful treatment in pregnancy outcome, 34,35,47 supports an implication of this molecule in cell proliferation process.…”

Section: Numbermentioning

confidence: 81%

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HLA‐F transcriptional and protein differential expression according to its genetic polymorphisms

Paganini¹,

Faux

Beley

et al. 2023

HLA

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Many specificities single out HLA‐F: its structure, expression regulation at cell membrane and function. HLA‐F mRNA is detected in the most cell types and the protein is localized in the ER and Golgi apparatus. When expressed at cell surface, HLA‐F may be associated to β2‐microglobulin and peptide or expressed as an open‐conformer molecule. HLA‐F reaches the membrane upon activation of different primary cell types and cell‐lines. HLA‐F has its highest affinity for the KIR3DS1‐activating NK receptor, but also binds inhibitory immune receptors. Some studies reported that HLA‐F expression is associated with its genotype. Higher HLA‐F mRNA expression associated with F*01:01:02, and 3 noncoding SNPs, rs1362126, rs2523405, and rs2523393, located in HLA‐F‐AS1 or upstream the HLA‐F sequence were associated with HLA‐F mRNA expression. Given the implication of HLA‐F in many clinical setting, and the undisclosed process of its expression regulation, we aim to confirm the effect of the aforementioned SNPs with HLA‐F transcriptional and protein expression. We analyzed the distribution, frequency and linkage disequilibrium of these SNPs at worldwide scale in the 1000 Genomes Project samples. Influence on the genotype of each SNP on HLA‐F expression was explored using RNAseq data from the 1000 Genomes Project, and using Q‐PCR and intracellular cytometry in PBMC from healthy individuals. Our results show that the SNPs under studied displayed remarkably different allelic proportion according to geography and confirm that rs1362126, rs2523405, and rs2523393 displayed the most concordant results, with the highest effect size and a double‐dose effect.

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Section: Discussionmentioning

confidence: 90%

Section: Numbermentioning

confidence: 81%

HLA‐F transcriptional and protein differential expression according to its genetic polymorphisms

Paganini¹,

Faux

Beley

et al. 2023

HLA

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“…HLAF protein is encoded by the HLA-F gene. HLA-F was significantly upregulated in glioblastoma samples, 28 and its expression was positively correlated with malignant phenotype and negatively correlated with overall survival of glioblastoma. 29 Interestingly, in contrast to the EPC2 (E7ov) results described above, the K2C8 protein encoded by the KRT8 gene was the most dramatically downregulated protein in KYSE30 (E7ov) cells.…”

Section: Underlying Mechanism For Hpv16 E6 and E7 Genes In Escc Cells...mentioning

confidence: 98%

HPV16 infection promotes the malignant transformation of the esophagus and progression of esophageal squamous cell carcinoma

Zhao,

Wei,

Zhang

et al. 2023

Journal of Medical Virology

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Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.

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“…HLA staining that visualizes mostly glioma infiltrating myeloid cells that accumulate in the tumor has been proven to play an important role in glioblastoma biology and can be used as a diagnostic biomarker. 19 Fan et. al showed increased HLA-DR score in more aggressive stages of glioma.…”

Section: Introductionmentioning

confidence: 99%

Automated glioma multiclass tumor classification

Pytlarz¹,

Wojnicki

Pilanc-Kudlek³

et al. 2023

Medical Imaging 2023: Digital and Computational Pathology

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Gliomas are primary brain tumors that arise from neural stem cells or glial precursors. Diagnosis of glioma is based on histological evaluation of pathological cell features and some molecular markers. Gliomas are infiltrated by myeloid cells that accumulate preferentially in malignant tumors and their abundance inversely correlates with survival, which is of interest for cancer immunotherapies. To avoid time-consuming and laborious manual examination of the images, a deep learning approach for automatic multiclass classification of tumor grades was proposed. Moreover, the challenge of the study was given by small sample size of human leukocyte antigen tissue microarrays dataset (HLA-TMA) - total 204 images from 5 classes - and imbalanced data distribution. This has been addressed by images augmentation of the underrepresented classes, as already shown in a similar study about predicting mutations from glioma biopsies.1 For this glioma multiclass classification task, the architecture of residual neural network has been adapted. The best model produced an accuracy score of 0.7727, and the mean accuracy of the cross-validation iterations was the value of 0.7248 on the validation set. This promising approach can be used as an additional diagnostic tool to improve assessment during intra-operative examination or sub-typing tissues for treatment selection, despite the challenges presented by the difficult dataset.

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HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation

Cited by 12 publications

References 87 publications

HLA‐F transcriptional and protein differential expression according to its genetic polymorphisms

HLA‐F transcriptional and protein differential expression according to its genetic polymorphisms

HPV16 infection promotes the malignant transformation of the esophagus and progression of esophageal squamous cell carcinoma

Automated glioma multiclass tumor classification

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