HLA-G expression in human ovarian carcinoma counteracts NK cell function

Lin, Aifen; Yan, Wei‐Hua; Xu, Haiyun; Gan, Meifu; Cai, Jiahui; Zhu, Min; Zhou, Mengya

doi:10.1093/annonc/mdm356

Cited by 91 publications

(78 citation statements)

References 24 publications

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“…[40][41][42] In our cohort, upregulation of nonclassical MHC Class I (HLA-G) was observed in 39.8% of samples (209/525; 95% CI: 35.6-44.0). A study by Barrier et al, 27 using comparable staining techniques and the same mAB, described HLA-G expression in 55% (24/44 of endometrial cancer samples).…”

Section: Discussionmentioning

confidence: 75%

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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Section: Discussionmentioning

confidence: 75%

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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“…HLGA-G5 type has been detected in tumor while soluble form of HLA-G was found in ascites [107,108] and in the blood of patients [109]. HLA-G seems to be implicated in the immune response modulation through NKT cell inhibition [110]. In the tumor cells expressing a B7 co-stimulatory family molecule, B7H4 is known to inhibit antigen-dependent induction of T cell proliferation and activation.…”

Section: Proteins Involved In Immune Response Modulationmentioning

confidence: 99%

Ovarian cancer molecular pathology

Longuespée

Boyon

Desmons

et al. 2012

Cancer Metastasis Rev

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Ovarian cancer (OVC) is the fourth leading cause of cancer mortality among women in Europe and the United States. Its early detection is difficult due to the lack of specificity of clinical symptoms. Unfortunately, late diagnosis is a major contributor to the poor survival rates for OVC, which can be attributed to the lack of specific sets of markers. Aside from patients sharing a strong family history of ovarian and breast cancer, including the BRCA1 and BRCA2 tumor suppressor genes mutations, the most used biomarker is the Cancer-antigen 125 (CA-125). CA-125 has a sensitivity of 80 % and a specificity of 97 % in epithelial cancer (stage III or IV). However, its sensitivity is 30 % in stage I cancer, as its increase is linked to several physiological phenomena and benign situations. CA-125 is particularly useful for at-risk population diagnosis and to assess response to treatment. It is clear that alone, CA-125 is inadequate as a biomarker for OVC diagnosis. There is an unmet need to identify additional biomarkers. Novel and more sensitive proteomic strategies such as MALDI mass spectrometry imaging studies are well suited to identify better markers for both diagnosis and prognosis. In the present review, we will focus on such proteomic strategies in regards to OVC signaling pathways, OVC development and escape from the immune response.

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“…HLGA-G5 type has been detected in tumor and soluble form of HLA-G in ascites 54,55 and in the blood of patients 56 . HLA-G seems to be implicated in the immune response modulation through NKT cell inhibition 57 . In the tumor cells expressing a B7 costimulatory family molecule, B7H4 is known to inhibit antigen-dependent induction of T cell proliferation and activation.…”

Section: Proteins Involved In Immune Response Modulationmentioning

confidence: 99%