The clinicopathologic significance of the expression of HLA-G in oral squamous cell carcinoma

Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14-bp insertion/deletion (InDel) polymorphism in the 3' untranslated region (3'-UTR) of HLA-G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA-G (sHLA-G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57-0.99; p = 0.040). Distribution of the 14-bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33-0.99; p = 0.044) and the log-additive model (OR = 0.76; 95% CI: 0.58-0.99; p = 0.044). The serum sHLA-G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA-G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856-0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA-G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA-G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA-G 14-bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA-G may act as a promising biomarker for noninvasive diagnosis of OSCC.

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“…Overexpression of total HLA‐G protein in OSCC was found previously (Goncalves et al, ). But the serum sHLA‐G level in OSCC was largely unknown.…”

Section: Discussionsupporting

confidence: 68%

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Wang

Zhao

Liu

et al. 2018

Int J Immunogenetics

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“…However, more studies on the complete HLA-G gene and its linkage disequilibrium with other genes and on HLA-G expression at both the tumor site and plasma in a specific microenvironment are required to consolidate these findings. carcinoma (69,70), esophageal squamous cell carcinoma (71)(72)(73)(74), gastric cancer (75)(76)(77), glioblastoma (78), hepatocellular carcinoma (79)(80)(81), lung cancer (82)(83)(84), nasopharyngeal carcinoma (85), oral cavity squamous cell carcinoma (86), ovarian cancer (87-89), pancreatic adenocarcinoma (90), thyroid carcinoma (91,92). These data were summarized in Table 1.…”

Section: Relevance Of Hla-g Expression In Cancersmentioning

confidence: 99%

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Lin

Yan

2015

Mol Med

101

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Aberrant induction of human leukocyte antigen-G (HLA-G) expression has been observed in various malignancies and is strongly associated with tumor immune escape, metastasis and poor prognosis. To date, great achievements have been made in understanding the underlying mechanisms of HLA-G involved in tumor progression. HLA-G could lead to tumor evasion by inhibition of immune cell cytolysis, differentiation and proliferation and inhibition of cytokine production, induction of immune cell apoptosis, generation of regulatory cells and expansion of myeloid-derived suppressive cells and by impairment of chemotaxis. Moreover, HLA-G could arm tumor cells with a higher invasive and metastatic potential with the upregulation of tumor-promoting factor expression such as matrix metalloproteinases (MMPs), indicating that ectopic HLA-G expression could render multiple effects during the progression of malignancies. In this review, we summarized the mechanisms of HLA-G involved in promoting tumor cell immune escaping, metastasis and disease progression. Special attention will be paid to its significance as an attractive therapeutic target in cancers.

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“…HLA-G expression in the tumor invasive front was assessed by adapting the method proposed by Gonçalves et al 6 . Tumor cells that exhibited granular cytoplasmic brown staining were considered to be positive.…”

Section: Analysis Of the Immunohistochemical Profilementioning

confidence: 99%

“…the immune escape mechanisms utilized by tumor cells is the expression of human leukocyte antigen G (HLA-G). 4,5,6 HLA-G is a nonclassical major histocompatibility complex (MHC) molecule and it is located on the short arm of chromosome 6 at 6p21.31. It is characterized by limited polymorphism, expression restricted to some tissues, and alternative splicing that leads to the production of seven different isoforms -four membrane-bound (HLA-G1 to G4) and three soluble isoforms (HLA-G5 to G7).…”

Section: Introductionmentioning

confidence: 99%

“…A few studies have associated a larger amount of Treg cells in malignant neoplasms with antitumor immune response evasion and, consequently, with a worse prognosis. 17,18 Investigations about the role of HLA-G in oral cancer microenvironment and its relationship with clinical parameters is still lacking in the literature 6,11,19 and, to date, there have been no investigations into the relationship between HLA-G and FoxP3+ Treg cells in these tumors. Therefore, the aim of the present study was to assess HLA-G expression in tumor cells and in FoxP3+ Treg cells in oral tongue and lower lip squamous cell carcinomas (SCCs), tumors with different behaviors and prognoses, and to verify its relationship with clinical parameters.…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas

et al. 2019

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Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

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The clinicopathologic significance of the expression of HLA-G in oral squamous cell carcinoma

Cited by 26 publications

References 29 publications

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas

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