Expression of Human Leukocyte Antigen G (HLA-G) Correlates with Poor Prognosis in Gastric Carcinoma

Yie, Shang-mian; Zhang, Pengcheng; Ye, Shang-rong; Li, Ké; Dong, Di; Lin, Xinmei

doi:10.1245/s10434-007-9464-y

Cited by 91 publications

(94 citation statements)

References 37 publications

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“…28 Other studies also revealed that there was significant correlation between HLA-G expression and poor clinical outcomes in lung, gastric and colorectal tumors. 26,31,32 In the context of ESCC, a previous study revealed that HLA-G was expressed in 90.9% (110/121) of the primary sites of ESCC, which is much higher than that observed in our study (65.8%, 52/79). 36 The difference between our data and that study might be caused by the staining evaluation method and antibodies used in the studies.…”

Section: Discussioncontrasting

confidence: 86%

“…Besides the antibody HGY applied to evaluate the HLA-G expression in ESCC, other malignancies such as NSCLC (HLA-G positive staining: 79/106, 75.0%), gastric cancer (113/160, 71%) and colorectal cancer (130/201, 65%) were also investigated by the same group. 26,31,32 HLA-G positive percentage in these studies was prone to be higher than that in other studies such as colorectal cancer (mAb 4H84, 52/ 100, 52%, p ¼ 0.03), 39 ).…”

Section: Tumor Immunologycontrasting

confidence: 63%

“…23 It has also been reported that the status of HLA-G expression or sHLA-G levels in plasma was correlated with certain clinicopathological parameters in malignancies such as hepatocellular carcinoma (HCC), 24,25 nonsmall-cell lung cancer (NSCLC), 15,26,27 breast cancer, 28 endometrial carcinoma, 29 B-cell chronic lymphocytic leukemia (B-CLL), 30 gastric carcinoma and colorectal cancer. 31,32 These studies indicated that HLA-G might serve as a clinical marker in the diagnosis or prediction of clinical outcomes for malignant diseases. Esophageal carcinoma is one of the most malignant diseases and has a poor prognosis that only 17% of the cases in the United States survive at least 5 years at present.…”

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confidence: 99%

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Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

Lin

Zhang

Zhou

et al. 2011

Intl Journal of Cancer

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Human leukocyte antigen (HLA)‐G inhibits functions of immune component cells and promotes malignant cells evading from antitumor immunity. We investigated the clinical relevance of HLA‐G expression in esophageal squamous cell carcinoma (ESCC). In our study, HLA‐G expression in 79 primary ESCC lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Soluble HLA‐G (sHLA‐G) in plasma was detected with enzyme‐linked immunosorbent assay (ELISA) in 41 ESCC patients (including 19 case‐matched lesions and plasma samples) and in 153 normal healthy controls. HLA‐G expression was observed in 65.8% (52/79) of the ESCC lesions but not in adjacent normal esophageal tissues. HLA‐G expression was more frequently observed in patients with advanced disease stage (III/IV vs. I/II, p = 0.01). Patients with HLA‐G expression had a significantly worse survival, and HLA‐G could be an independent prognostic factor. sHLA‐G levels in plasma were significantly increased in patients compared to normal controls (median: 152.4 U/ml vs. 8.9 U/ml, p < 0.001). The area under receiver‐operating characteristic (ROC) curve for sHLA‐G in plasma was 0.992. However, no significant correlation was found between sHLA‐G in plasma and clinical parameters studied. In conclusion, our findings indicated that HLA‐G expression in ESCC is associated with poor survival and could be a prognostic indicator. Furthermore, increased levels of sHLA‐G in plasma might be a useful preoperative biomarker for diagnosis.

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Section: Discussioncontrasting

confidence: 86%

Section: Tumor Immunologycontrasting

confidence: 63%

mentioning

confidence: 99%

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Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

Lin

Zhang

Zhou

et al. 2011

Intl Journal of Cancer

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“…[19][20][21][22][23] Correlation between poor clinical outcome and HLA-G expression in gastric 24 and colorectal tumors 25 and in B-cell chronic lymphocytic leukemia 26 shows that HLA-G might be used as a prognostic marker. In a small cohort of patients with endometrial cancer a correlation was observed between HLA-G expression and stage of disease.…”

mentioning

confidence: 99%

The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

Bijen

Bantema-Joppe

Jong

et al. 2010

Intl Journal of Cancer

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The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-G]) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and nonclassical MHC class I using the following monoclonal antibodies: 4H84 (anti-HLA-G), b2-m (anti-beta-2-microglobulin) and HC-10 (MHC class I antigen heavy chain). Expression data were linked to known clinicopathological characteristics and survival. HLA-G upregulation and MHC class I downregulation in neoplastic cells was observed in 40% and 48%, respectively. Nonendometrioid tumor type, advanced stage disease (FIGO stage !II) and poorly or undifferentiated tumors were associated with MHC class I downregulation. Absence of HLA-G expression was independently associated with MHC class I downregulation. In univariate analysis, MHC class I downregulation was a predictor of worse disease-specific survival. Prognostic unfavorable tumor characteristics were correlated with downregulation of MHC class I expression in endometrial cancer cells. Furthermore, downregulated MHC class I has a negative impact on diseasespecific survival, observed in a large cohort of patients with endometrial cancer. As there seems to be a relation between classical and nonclassical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism.Endometrial adenocarcinoma is the most common gynecological malignancy in the developed world.1 In The Netherlands, 1,400 women are diagnosed with endometrial cancer each year, of which the majority is an early stage of disease. Prognosis is good in low-stage endometrial cancer (5-year survival International Federation of Gynecology and Obstetrics [FIGO] Stages I and II: 86% and 66%), but it decreases rapidly in higher stages (5-year survival FIGO Stages III and IV: 44% and 16%).2 Nonendometrioid histological type or Grade 3 endometrioid carcinoma (Type II tumors) have been identified as prognostically worse subgroups.3 Classical surgical approaches in combination with radiotherapy and/or chemotherapy have had only limited success in improving the overall survival in Type II endometrial cancer. In future, immunotherapy might fulfill a role in the treatment of endometrial cancer. Additional investigation is warranted to show that the immune system does play a (prognostic) role in this type of cancer. 4,5 Major histocompatibility complex (MHC) Class I expression might be such a cell surface marker with prognostic significance in endometrial cancer, exemplifying the role of the cellular immune system.All human body cells present antigens to the immune system by means of MHC Class I molecules on the cell surface. MHC Class I antigens comprise the classical (Class Ia) human leukocyte antigen (HLA)-A, -B and -C antigens and the nonclassical (Class Ib) HLA-E...

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“…[12][13][14] Indeed, HLA-G tumor expression is associated with poor prognosis for some malignancies. [15][16][17] Epigenetic factors such as DNA methylation are involved in the regulation of HLA-G expression and demethylating agents such as 5-aza-2 0 -deoxycytidine (5-AZA) can enhance HLA-G expression in leukemias. 18,19 Because of its immune-suppressive activity and its tissue-restricted expression, it is possible that HLA-G could function as a TAA for developing T cell-based immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy

et al. 2016

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(2016) Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy, OncoImmunology, 5:6, e1169356 ABSTRACTTumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4 C helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8 C cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G 26-40 was effective in eliciting tumor-reactive CD4 C T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2 0 -deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G 26-40 -specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.

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Expression of Human Leukocyte Antigen G (HLA-G) Correlates with Poor Prognosis in Gastric Carcinoma

Abstract: Overall, our results indicated that the expression of HLA-G is a characteristic feature of gastric carcinoma and that immunostaining by anti-HLA-G antibody may be a potentially useful prognostic indicator.

Cited by 91 publications

References 37 publications

Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy

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