Melanomas and melanoma cell lines do not express HLA‐G, and the expression cannot be induced by γIFN treatment

Frumento, Guido; Franchello, S.; Palmisano, Giulio Lelio; Nicotra, Maria Rita; Giacomini, Patrizio; Loke, Y.W.; Geraghty, Daniel E.; Maio, Michele; Manzo, Ciro; Natali, P. G.; Ferrara, G. B.

doi:10.1034/j.1399-0039.2000.560104.x

Cited by 49 publications

(24 citation statements)

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“…It is possible that the antibody and technique used do not allow to detect all HLA-G expression in cytoplasm and at cell surface. 43,44 However, immunohistochemistry of fresh-frozen tissue as well as paraffin-embedded tissue showed similar staining patterns of HLA-G expression. Furthermore, a magnified picture of strong HLA-G expression on paraffin tissue clearly showed membrane staining (see Fig.…”

Section: Discussionmentioning

confidence: 90%

“…Concerning HLA-G expression and cancer, only 3 reports were published which showed absence or low frequency of HLA-G expression. 43,44,46 This might suggest the possibility of either a publication bias or a systematic difference between smaller and larger studies. As there is a relationship between effect and study size, we believe that our negative outcome for HLA-G performed in a large cohort of patients is of major importance.…”

Section: Discussionmentioning

confidence: 99%

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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: 90%

Section: Discussionmentioning

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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“…3), thus strongly corroborating our functional in vitro observations in glioma. Although to date ectopic expression of HLA-G has been demonstrated in some tumors (32)(33)(34)(35)(36), the overall relevance of this molecule as an alternative principle of tumor immune escape remains controversial (37)(38)(39)(40), an issue that is further complicated by the limitations of available Abs to detect HLA-G expression in vivo (41,42).…”

Section: Discussionmentioning

confidence: 99%

A Functional Role of HLA-G Expression in Human Gliomas: An Alternative Strategy of Immune Escape

Wiendl¹,

Mitsdoerffer²,

Hofmeister

et al. 2002

The Journal of Immunology

294

220

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HLA-G is a nonclassical MHC molecule with highly limited tissue distribution that has been attributed chiefly immune regulatory functions. Glioblastoma is paradigmatic for the capability of human cancers to paralyze the immune system. To delineate the potential role of HLA-G in glioblastoma immunobiology, expression patterns and functional relevance of this MHC class Ib molecule were investigated in glioma cells and brain tissues. HLA-G mRNA expression was detected in six of 12 glioma cell lines in the absence of IFN-γ and in 10 of 12 cell lines in the presence of IFN-γ. HLA-G protein was detected in four of 12 cell lines in the absence of IFN-γ and in eight of 12 cell lines in the presence of IFN-γ. Immunohistochemical analysis of human brain tumors revealed expression of HLA-G in four of five tissue samples. Functional studies on the role of HLA-G in glioma cells were conducted with alloreactive PBMCs, NK cells, and T cell subpopulations. Expression of membrane-bound HLA-G1 and soluble HLA-G5 inhibited alloreactive and Ag-specific immune responses. Gene transfer of HLA-G1 or HLA-G5 into HLA-G-negative glioma cells (U87MG) rendered cells highly resistant to direct alloreactive lysis, inhibited the alloproliferative response, and prevented efficient priming of cytotoxic T cells. The inhibitory effects of HLA-G were directed against CD8 and CD4 T cells, but appeared to be NK cell independent. Interestingly, few HLA-G-positive cells within a population of HLA-G-negative tumor cells exerted significant immune inhibitory effects. We conclude that the aberrant expression of HLA-G may contribute to immune escape in human glioblastoma.

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“…Again, the authors found all melanoma cell lines tested to be negative for HLA-G protein expression. At least, a recent study of Frumento et al [10] demonstrated the lack of expression of HLA-G protein in all but one out of a large panel of 45 melanoma cell lines, constitutively as well as after treatment with IFN-γ, as well as in 8 melanoma tissue specimens. Such results as contrary as in all these studies dealing with HLA-G protein expression in melanoma might be due to the use of mAbs unreactive in the application of immunohistochemistry or flow cytometry.…”

Section: Expression Of Hla-g In Malignant Melanomamentioning

confidence: 99%

“…Thus, neoplastic cells of different origin were recently examined for their expression of HLA-G, revealing malignant melanoma as the first solid tumor that was described to express this nonclassical HLA molecule and, moreover, due to this expression was protected from NK cell lysis [8]. However, further investigations by other workgroups revealed contrary results [9,10], leaving the question of an expression of HLA-G in cancer cells as a subject of ongoing debate.…”

Section: Introductionmentioning

confidence: 99%

HLA-G in Melanoma: A New Strategy to Escape from Immunosurveillance?

2002

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The non-classical HLA class-I molecule HLA-G, primarily expressed on fetal cells of the human placenta, has been shown to play a crucial role in maintaining an immuno-privileged environment at the materno-fetal interface. Fetal trophoblast cells are protected from attack by CD8+ cytotoxic T lymphocytes due to their lacking expression of classical HLA class-I molecules, again rendering them susceptible to natural killer (NK) cell lysis. HLA-G has been shown to interact with killing inhibitory receptors, hereby rescuing the fetal placenta cells from NK cell attack. Likewise, classical HLA class-I molecules are known to be frequently downregulated or lost during the development of malignancies. This abnormality is often associated with a poor clinical course of disease, despite of the frequent detection of tumor-infiltrating NK cells. This controversy seemed to be resolved with the detection of HLA-G expression on cells of malignant melanoma and other solid tumors. Since interferon(IFN)s are known for their ability of upregulation or induction of HLA-G expression, the potential function of HLA-G as a new strategy of cancer cells to escape from immunosurveillance might be of particular importance in malignant melanoma. The frequent use of IFN-α in the immunotherapy of this malignancy might possibly worsen the already impaired antitumoral immune response state of melanoma patients. However, several studies recently failed to detect any HLA-G protein expression in cancer cell lines and tissues of different origin, particularly in malignant melanoma, yet rendering the expression and function of HLA-G in malignancies as a possibly overrated matter of controversial debate.

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Melanomas and melanoma cell lines do not express HLA‐G, and the expression cannot be induced by γIFN treatment

Cited by 49 publications

References 21 publications

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

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

A Functional Role of HLA-G Expression in Human Gliomas: An Alternative Strategy of Immune Escape

HLA-G in Melanoma: A New Strategy to Escape from Immunosurveillance?

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