The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

Xu, Huihui; Yan, Wei‐Hua; Lin, Aifen

doi:10.3389/fimmu.2020.01349

Cited by 25 publications

(32 citation statements)

References 126 publications

(206 reference statements)

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“…Our in vivo study provided that blocking HLA-G with a specific neutralizing antibody can inhibit the growth of HLA-G-positive tumor cells and restore antitumour immunity against HLA-G-positive tumor cells in a humanized mouse model of ovarian cancer (70). In humans, we have widely studied the relationship between HLA-G expression and clinical outcomes in different tumor types, including solid tumors (3,4,(68)(69)(70)(71)(72)(73)(74)(75)(76)(77) and hematologic malignancies (78,79). Our previous studies also explored the regulation mechanisms of HLA-G expression and function (80)(81)(82).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers

Gan

et al. 2021

Front. Immunol.

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Human leukocyte antigen G (HLA-G) is known as a novel immune checkpoint molecule in cancer; thus, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. The aim of this study was to systematically identify the roles of checkpoint HLA-G molecules across various types of cancer. ONCOMINE, GEPIA, CCLE, TRRUST, HAP, PrognoScan, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, STRING, GeneMANIA, DAVID, TIMER, and CIBERSORT were utilized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In this study, we comprehensively analysed the heterogeneous expression of HLA-G molecules in various types of cancer and focused on genetic alterations, coexpression patterns, gene interaction networks, HLA-G interactors, and the relationships between HLA-G and pathological stage, prognosis, and tumor-infiltrating immune cells. We first identified that the mRNA expression levels of HLA-G were significantly upregulated in both most tumor tissues and tumor cell lines on the basis of in-depth analysis of RNAseq data. The expression levels of HLA-G were positively associated with those of the other immune checkpoints PD-1 and CTLA-4. Abnormal expression of HLA-G was significantly correlated with the pathological stage of some but not all tumor types. There was a significant difference between the high and low HLA-G expression groups in terms of overall survival (OS) or disease-free survival (DFS). The results showed that HLA-G highly expressed have positive associations with tumor-infiltrating immune cells in the microenvironment in most types of tumors (P<0.05). Additionally, we identified the key transcription factor (TF) targets in the regulation of HLA-G expression, including HIVEP2, MYCN, CIITA, MYC, and IRF1. Multiple mutations (missense, truncating, etc.) and the methylation status of the HLA-G gene may explain the differential expression of HLA-G across different tumors. Functional enrichment analysis showed that HLA-G was primarily related to T cell activation, T cell regulation, and lymphocyte-mediated immunity. The data may provide novel insights for blockade of the HLA-G/ILT axis, which holds potential for the development of more effective antitumour treatments.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers

Gan

et al. 2021

Front. Immunol.

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“…HLA-G can interact with immunoglobulin-like proteins on dendritic cells (DC) (39,40), and through such self-made interactions, can suppress immune cells (41). Importantly, in normal tissues, HLA-G is most abundantly distributed on the surface of trophoblast cells in the placenta, which can effectively inhibit the local immune response in the uterus and promote the tolerance of the mother to the foetus (6,42). Based on this characteristic, the expression level of HLA-G is closely related to the success rate of embryo transfer during IVF treatment.…”

Section: Discussionmentioning

confidence: 99%

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

Wang

Yao

2021

Ann Transl Med

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Background: The human leukocyte antigen G5 subtype (HLA-G5) is a major histocompatibility complex (MHC) molecule that is selectively expressed at the maternal-foetal tissue interface and is required for the successful implantation of the in vitro fertilized embryo. It is critical to detect HLA-G5, especially HLA-G5 expression in embryo fluid, during in vitro embryo incubation and culture. However, the specificity and sensitivity of traditional ELISA methods to detect sHLA-G5 are insufficient. This work aimed to explore novel nucleic acid aptamer gold (Au)-nanoparticles to detect soluble HLA-G5 in liquid samples.Methods: Soluble HLA-G5 was obtained using a prokaryotic expression system, and two novel aptamers (HLA-G5-Apt1 and HLA-G5-Apt2) detecting HLA-G5 were screened by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. Small (10 nm) gold nanoparticles (AuNPs) were incubated with AptHLAs to form two novel nucleic acid aptamers: Au-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2). Results:The results showed that AptHLA-G5-1 and AptHLA-G5-2 have a high affinity for HLA-G5 and can detect its presence in liquid samples. Using the colorimetric sensing method, AuNPs-AptHLA-G1 had a detection limit as low as 20 ng/mL (recovery range between 98.7% to 102.0%), while AuNPs-AptHLA-G2 had a detection limit as low as 20 ng/mL (recovery range between 98.9% to 103.6%).Conclusions: Our work demonstrates that novel AuNPs are efficient detectors for HLA-G5 and are useful for diagnosis and treatment in the field of obstetrics-gynaecology.

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“…In the past three decades, a large number of candidate gene studies for identifying genes conferring susceptibility to cervical cancer have been reported. Genetic variants in the HLA region have been extensively studied in gene association studies of HPV neoplasm and also the strongest associations with cervical neoplasia are with HLA genes, where both risk and protective alleles have been identified [8,[42][43][44]. A recent meta-analysis of 36 case-control studies (6645 cases and 9095 controls), revealed multiple HLA-DRB1 alleles associated with cervical cancer in women of diverse ancestry populations.…”

Section: Genetic Variants and Hpv-induced Cervical Cancermentioning

confidence: 99%

Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers

Espinoza

Pham

et al. 2021

Microorganisms

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Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers. Previous studies have quantified that heritability, in the form of genetic variants, common in the general population, is implicated in nearly 30% of cervical cancers and a large number of studies conducted across various populations have identified genetic variants that appear to be associated with genes that predispose or protect the host to HPV infections thereby affecting individual susceptibility to HPV-associated cancers. In this article, we provide an overview of gene association studies on HPV-associated cancers with emphasis on genome-wide association study (GWAS) that have identified novel genetic factors linked to HPV infection or HPV-associated cancers.

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The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

Cited by 25 publications

References 126 publications

Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers

Comprehensive Transcriptomic Analysis Reveals the Role of the Immune Checkpoint HLA-G Molecule in Cancers

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers

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