Switch ofHLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

Rouas‐Freiss, Nathalie; Bruel, Sylvie; Menier, Catherine; Marcou, Céline; Moreau, Philippe; Carosella, Edgardo D.

doi:10.1002/ijc.21151

Cited by 56 publications

(59 citation statements)

References 51 publications

(75 reference statements)

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“…18 M8 cells transfected with the pcDNA3.1 vector alone were used as a negative control (M8-pcDNA), as described previously. The cell lines Fon, a tumor cell line naturally expressing HLA-G, 19 and YAC-1, a murine T-lymphoma cell line (ATCC) were maintained in complete medium.…”

Section: Cell Culturementioning

confidence: 99%

“…Whereas the primary culture cell line exhibited a high level of HLA-G1 cell-surface expression (Fon ϩ cells), this was completely lost during long-term in vitro propagation (Fon Ϫ cells; Figure 7A inset). 19 We subcutaneously injected 10 ϫ 10 6 Fon Ϫ or Fon ϩ cells and performed the same experiments as described for M8 cells. 10 ϫ 10 6 Fon ϩ cells expressing HLA-G1 grew rapidly under the skin of Balb/c mice, whereas Fon Ϫ cells were rejected immediately ( Figure 7A).…”

Section: Tumors Expressing Constitutively Hla-g Grow In Immunocompetementioning

confidence: 99%

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Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17

Agaugué

Carosella

Rouas‐Freiss

2011

Blood

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120

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Section: Cell Culturementioning

confidence: 99%

Section: Tumors Expressing Constitutively Hla-g Grow In Immunocompetementioning

confidence: 99%

Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17

Agaugué

Carosella

Rouas‐Freiss

2011

Blood

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120

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“…HLA-G inhibits the functions of NK cells and cytotoxic T-lymphocytes (CTLs; reviewed in Carosella et al 15 ), inhibits allogeneic responses, 16,17 induces regulatory cells, [16][17][18] up-regulates inhibitory receptor expression, 19 and inhibits dendritic-cell maturation. 18 This has positioned HLA-G as a molecule capable of significantly contributing to tolerance of allografts 17,20,21 and immune escape of tumors [22][23][24][25][26] and virus-infected cells. 27,28 In pathologic contexts, HLA-G is often expressed by antigenpresenting cells that infiltrate lesions (reviewed in Carosella et al 15 ).…”

Section: Introductionmentioning

confidence: 99%

Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells

LeMaoult

Caumartin

Daouya

et al. 2006

Blood

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238

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Trogocytosis is the uptake of membrane fragments from one cell by another and has been described for immune cells in mice and humans. Functional consequences of trogocytosis are emerging, but a dramatic immune function has still to be associated with it. Here we show that some resting, and most activated, CD4 ؉ and CD8 ؉ T cells acquire immunosuppressive HLA-G1 from antigen-presenting cells (APCs) in a few minutes. Acquisition of HLA-G through membrane transfers does not change the real nature of the T cells but immediately reverses their function from effectors to regulatory cells. These regulatory cells can inhibit allo-proliferative responses through HLA-G1 that they acquired. These data demonstrate that trogocytosis of HLA-G1 leads to instant generation of a new type of regulatory cells, which act through cell-surface molecules they temporarily display but do not express themselves. Such regulatory cells whose existence is most likely limited in space and time might constitute an "emergency" immune suppression mechanism used by HLA-G-expressing tissues to protect themselves against immune aggression. In addition, T cells acquire from HLA-Gexpressing APCs their HLA-G-dependent capability to induce the slower differentiation of regulatory cells that act independently of HLA-G. These data re-emphasize the significance of HLA-G expression in normal and pathologic situations. Introduction"Trogocytosis" is a new name for "fast, cell-to-cell contactdependent uptake of membranes and associated molecules." 1 Trogocytosis has been documented in T and B lymphocytes, natural killer (NK) cells, antigen-presenting cells (APCs), and tumor cells (reviewed in Hudrisier and Bongrand 2 ). Most of the work on trogocytosis by T cells was done in the murine system, in which it was shown that CD4 ϩ and CD8 ϩ T cells acquired APC major histocompatibility complex (MHC) class II and MHC class I molecules, respectively, in an antigen-specific manner [3][4][5][6][7] : for trogocytosis to occur, T-cell receptor (TCR) engagement was necessary, and activation or anti-CD3 increased trogocytosis efficiency. 8,9 Yet, there is no strict dependence of trogocytosis on TCR engagement: (1) in some systems, trogocytosis was shown to depend on CD28 engagement 5 ; and (2) transfer of MHC class II antigens from APCs to T cells can occur in an all-autologous system. 8 Even though most of the work on APC material acquisition by T cells was done on MHC molecules, it was shown that costimulatory molecules B7-1 (CD80), B7-2 (CD86), and ICAM-1 (CD54) are also acquired by murine antigen-specific T cells. 5,10 Trogocytosis is a transfer of membrane fragments, not of individual molecules. Consequently, all molecules contained within a certain membrane area are transferred from one cell to another during trogocytosis, including some that might have nothing to do with the acquirer cell, or participate in cell-to-cell cross-talk. Thus, during trogocytosis, some molecules transfer passively. This was clearly evidenced by showing that CD8 ϩ T cells can acquire MH...

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“…HLA-G appears an attractive molecular target to develop new antitumor therapies. The reverse of tumor growth might be obtained through blockade of HLA-G synthesis by preventing its transcription using silencing RNA or acting on HLA-G alternative splicing [40], or through restoration of host immune responses using antibodies neutralizing interactions between HLA-G and its receptors [26]. …”

Section: Discussionmentioning

confidence: 99%

HLA-G Expression as a Prognostic Indicator in B-Cell Chronic Lymphocytic Leukemia

et al. 2014

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Background: The expression of human leukocyte antigen (HLA)-G was studied in certain malignancies and its role in escaping from immunosurveillance in cancers was proposed since HLA-G is a non-conventional HLA class I molecule that protects the fetus from immunorecognition during pregnancy. Some particles involved in the regulation of an immune system might represent prognostic value for B-cell chronic lymphocytic leukemia (B-CLL). The identification of novel prognostic factors in B-CLL may help define patient subgroups that may benefit from early therapeutic intervention. Objective: To evaluate the prognostic significance of HLA-G expression in B-CLL patients and its relationship with other well-established prognostic markers. Methodology: Thirty B-CLL patients diagnosed by clinical, morphological and immunophenotyping criteria were studied for HLA-G expression by flow cytometry. The relationship between HLA-G expression and some known prognostic markers was evaluated. Results: HLA-G was expressed in 36.7% of CLL patients at diagnosis, with a mean expression level of 35.31 ± 12.35%. A significant association between HLA-G expression and common prognostic markers of progressive disease was detected. The group of patients with positive HLA-G expression showed significantly higher absolute lymphocyte counts and serum levels of LDH and β₂-microglobulin, lower platelet counts, positive CD38 expression and advanced stages of Binet clinical staging. Conclusion: The present study demonstrated that HLA-G expression correlates with prognostic markers of a poor B-CLL outcome, mainly Binet clinical staging and CD38 expression by B-CLL cells, which indicates that this parameter may play a role as an important prognosticator of disease progression and consequently targeted therapy in B-CLL.

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Switch ofHLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

Cited by 56 publications

References 51 publications

Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17

Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17

Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells

HLA-G Expression as a Prognostic Indicator in B-Cell Chronic Lymphocytic Leukemia

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