The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Edgardo D Carosella - One of the best experts on this subject based on the ideXlab platform.
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HLA G proteins in cancer do they provide tumor cells with an escape mechanism
Cancer Research, 2005Co-Authors: Nathalie Rouasfreiss, Philippe Moreau, Soldano Ferrone, Edgardo D CarosellaAbstract:ConvincinG clinical evidence indicates that the limited success of T-cell-based immunotherapy of maliGnant diseases is caused, at least in part, by the ability of maliGnant cells to escape from immune recoGnition and destruction. AmonG the multiple escape mechanisms identified, a major role is played by chanGes in the expression and/or function of HLA antiGens expressed by tumor cells, because they may markedly affect tumor cell-host's immune system interactions. In this article, we review the data about the aberrant expression of the nonclassical HLA class I antiGen HLA-G by tumor cells. Furthermore, we discuss the possible reasons for the conflictinG information in the literature about HLA-G antiGen expression by maliGnant cells. Lastly, in liGht of the well-documented immunotolerant function of HLA-G, we discuss the potential role of these antiGens in the escape of tumor cells from immune recoGnition and destruction and in the clinical course of maliGnant diseases.
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analysis of HLA antiGen expression in beniGn and maliGnant melanocytic lesions reveals that upreGulation of HLA G expression correlates with maliGnant transformation hiGh inflammatory infiltration and HLA a1 Genotype
International Journal of Cancer, 2004Co-Authors: El Cherif Ibrahim, Edgardo D Carosella, S Aractingi, Yves Allory, Francesco Borrini, Alain Dupuy, P Duvillard, Mariefrancoise Avril, Pascale PaulAbstract:Previous studies indicate that the nonclassical class I HLA-G antiGen, whose physioloGic expression is mainly restricted to placenta, is upreGulated in melanoma, renal carcinoma, lunG carcinoma, Glioblastoma and ovarian carcinoma, where its inhibitory effect on cytotoxic effector cells function is thouGht to participate in immune evasion by tumor cells. To define whether this expression was a specific feature of melanocytic maliGnant transformation, 174 paraffin-embedded melanocytic lesions includinG naevi, lentiGo, primary and metastatic melanomas were analyzed for HLA-G and other HLA class I and class II antiGen expression. HLA-G antiGen expression in melanocytic cells was found to be siGnificantly hiGher (p < 0.0003) in melanoma (22/79, 28%) than in naevi (1/70, 1.4%), suGGestinG that upreGulation of HLA-G is associated with maliGnant transformation in this cell type. Further identification of HLA-G antiGen expression in inflammatory infiltratinG cells results in an overall frequency of HLA-G expressinG cells that is hiGher in melanoma (28/79, 35.5%) than in naevi (5/60, 8.3%) or lentiGo (2/23, 8.7%). UpreGulation of HLA-G or HLA class II molecules in melanocytic cells thus appears as a better predictor of maliGnancy than classical HLA class I antiGen defects, which are often described as an important mechanism used by tumor cells to evade immune surveillance. Furthermore, HLA-G expression was electively found in lesions that exhibited a hiGh inflammatory infiltrate as well as in patients displayinG HLA-A1 Genotype. These findinGs may provide new insiGhts in the comprehension of tumor proGression and desiGn of therapeutic approaches aimed at enhancinG antitumor immune responses in melanoma patients.
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specific activation of the non classical class i histocompatibility HLA G antiGen and expression of the ilt2 inhibitory receptor in human breast cancer
The Journal of Pathology, 2002Co-Authors: Sophie Lefebvre, Edgardo D Carosella, J Dausset, Martine Antoine, Serge Uzan, Michael T Mcmaster, Pascale PaulAbstract:The HLA-G molecule is a non-classical HLA class I antiGen selectively expressed by trophoblastic cells that invade the maternal decidua durinG human preGnancy. HLA-G is believed to contribute to tolerance of the semi-alloGeneic fetus by inhibitinG maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investiGated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, usinG two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was siGnificantly more frequent in lesions that were hiGhly infiltrated by host immune cells, thus correlatinG HLA-G activation with inflammation. Further histoloGical and double-staininG immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltratinG CD68+ and CD8+ cells. RT-PCR analysis suGGested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (IG-like transcript 2) killinG inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-reGulated at hiGh frequencies in human breast cancer, where it may impair efficient anti-tumour immunity.
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specific activation of the non classical class i histocompatibility HLA G antiGen and expression of the ilt2 inhibitory receptor in human breast cancer
The Journal of Pathology, 2002Co-Authors: Sophie Lefebvre, Edgardo D Carosella, J Dausset, Martine Antoine, Serge Uzan, Michael T Mcmaster, Pascale PaulAbstract:The HLA-G molecule is a non-classical HLA class I antiGen selectively expressed by trophoblastic cells that invade the maternal decidua durinG human preGnancy. HLA-G is believed to contribute to tolerance of the semi-alloGeneic fetus by inhibitinG maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investiGated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, usinG two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was siGnificantly more frequent in lesions that were hiGhly infiltrated by host immune cells, thus correlatinG HLA-G activation with inflammation. Further histoloGical and double-staininG immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltratinG CD68+ and CD8+ cells. RT-PCR analysis suGGested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (IG-like transcript 2) killinG inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-reGulated at hiGh frequencies in human breast cancer, where it may impair efficient anti-tumour immunity. CopyriGht © 2001 John Wiley & Sons, Ltd.
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tumor specific up reGulation of the nonclassical class i HLA G antiGen expression in renal carcinoma
Cancer Research, 2001Co-Authors: El Cherif Ibrahim, Nadia Guerra, Mariejose Terrier Lacombe, Eric Angevin, Salem Chouaib, Edgardo D Carosella, Anne Caignard, Pascale PaulAbstract:HLA-G is a nonclassical class I antiGen mainly expressed at the maternofetal interface durinG preGnancy where it is thouGht to downmodulate maternal immune response aGainst the semialloGeneic fetus. Recent studies indicate that ectopic up-reGulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investiGated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antiGen is differentially expressed in carcinoma and normal renal cells and that up-reGulation of this antiGen in the tumor cells is more frequent than alterations of other MHC class I or class II antiGens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (α and β) and, in particular, type II (γ) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suGGest that HLA-G displays various functional features that allow down-modulation of immune response in vitro , we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.
Pascale Paul - One of the best experts on this subject based on the ideXlab platform.
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analysis of HLA antiGen expression in beniGn and maliGnant melanocytic lesions reveals that upreGulation of HLA G expression correlates with maliGnant transformation hiGh inflammatory infiltration and HLA a1 Genotype
International Journal of Cancer, 2004Co-Authors: El Cherif Ibrahim, Edgardo D Carosella, S Aractingi, Yves Allory, Francesco Borrini, Alain Dupuy, P Duvillard, Mariefrancoise Avril, Pascale PaulAbstract:Previous studies indicate that the nonclassical class I HLA-G antiGen, whose physioloGic expression is mainly restricted to placenta, is upreGulated in melanoma, renal carcinoma, lunG carcinoma, Glioblastoma and ovarian carcinoma, where its inhibitory effect on cytotoxic effector cells function is thouGht to participate in immune evasion by tumor cells. To define whether this expression was a specific feature of melanocytic maliGnant transformation, 174 paraffin-embedded melanocytic lesions includinG naevi, lentiGo, primary and metastatic melanomas were analyzed for HLA-G and other HLA class I and class II antiGen expression. HLA-G antiGen expression in melanocytic cells was found to be siGnificantly hiGher (p < 0.0003) in melanoma (22/79, 28%) than in naevi (1/70, 1.4%), suGGestinG that upreGulation of HLA-G is associated with maliGnant transformation in this cell type. Further identification of HLA-G antiGen expression in inflammatory infiltratinG cells results in an overall frequency of HLA-G expressinG cells that is hiGher in melanoma (28/79, 35.5%) than in naevi (5/60, 8.3%) or lentiGo (2/23, 8.7%). UpreGulation of HLA-G or HLA class II molecules in melanocytic cells thus appears as a better predictor of maliGnancy than classical HLA class I antiGen defects, which are often described as an important mechanism used by tumor cells to evade immune surveillance. Furthermore, HLA-G expression was electively found in lesions that exhibited a hiGh inflammatory infiltrate as well as in patients displayinG HLA-A1 Genotype. These findinGs may provide new insiGhts in the comprehension of tumor proGression and desiGn of therapeutic approaches aimed at enhancinG antitumor immune responses in melanoma patients.
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specific activation of the non classical class i histocompatibility HLA G antiGen and expression of the ilt2 inhibitory receptor in human breast cancer
The Journal of Pathology, 2002Co-Authors: Sophie Lefebvre, Edgardo D Carosella, J Dausset, Martine Antoine, Serge Uzan, Michael T Mcmaster, Pascale PaulAbstract:The HLA-G molecule is a non-classical HLA class I antiGen selectively expressed by trophoblastic cells that invade the maternal decidua durinG human preGnancy. HLA-G is believed to contribute to tolerance of the semi-alloGeneic fetus by inhibitinG maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investiGated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, usinG two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was siGnificantly more frequent in lesions that were hiGhly infiltrated by host immune cells, thus correlatinG HLA-G activation with inflammation. Further histoloGical and double-staininG immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltratinG CD68+ and CD8+ cells. RT-PCR analysis suGGested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (IG-like transcript 2) killinG inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-reGulated at hiGh frequencies in human breast cancer, where it may impair efficient anti-tumour immunity.
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specific activation of the non classical class i histocompatibility HLA G antiGen and expression of the ilt2 inhibitory receptor in human breast cancer
The Journal of Pathology, 2002Co-Authors: Sophie Lefebvre, Edgardo D Carosella, J Dausset, Martine Antoine, Serge Uzan, Michael T Mcmaster, Pascale PaulAbstract:The HLA-G molecule is a non-classical HLA class I antiGen selectively expressed by trophoblastic cells that invade the maternal decidua durinG human preGnancy. HLA-G is believed to contribute to tolerance of the semi-alloGeneic fetus by inhibitinG maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investiGated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, usinG two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was siGnificantly more frequent in lesions that were hiGhly infiltrated by host immune cells, thus correlatinG HLA-G activation with inflammation. Further histoloGical and double-staininG immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltratinG CD68+ and CD8+ cells. RT-PCR analysis suGGested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (IG-like transcript 2) killinG inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-reGulated at hiGh frequencies in human breast cancer, where it may impair efficient anti-tumour immunity. CopyriGht © 2001 John Wiley & Sons, Ltd.
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tumor specific up reGulation of the nonclassical class i HLA G antiGen expression in renal carcinoma
Cancer Research, 2001Co-Authors: El Cherif Ibrahim, Nadia Guerra, Mariejose Terrier Lacombe, Eric Angevin, Salem Chouaib, Edgardo D Carosella, Anne Caignard, Pascale PaulAbstract:HLA-G is a nonclassical class I antiGen mainly expressed at the maternofetal interface durinG preGnancy where it is thouGht to downmodulate maternal immune response aGainst the semialloGeneic fetus. Recent studies indicate that ectopic up-reGulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investiGated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antiGen is differentially expressed in carcinoma and normal renal cells and that up-reGulation of this antiGen in the tumor cells is more frequent than alterations of other MHC class I or class II antiGens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (α and β) and, in particular, type II (γ) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suGGest that HLA-G displays various functional features that allow down-modulation of immune response in vitro , we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.
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molecular and immunoloGic aspects of the nonclassical HLA class i antiGen HLA G evidence for an important role in the maternal tolerance of the fetal alloGraft
American Journal of Reproductive Immunology, 1998Co-Authors: Philippe Moreau, Pascale Paul, Nathalie Rouasfreiss, Marek Kirszenbaum, J Dausset, Edgardo D CarosellaAbstract:PROBLEM: Human leukocyte antiGen (HLA)-G is a major histocompatibility complex class I antiGen, which is referred to as nonclassical because it displays a tissue-restricted distribution in the placenta, a reduced cytoplasmic domain, a limited polymorphism, and several isoforms. The HLA-G antiGen is thouGht to play an essential role durinG preGnancy by protectinG the semi-alloGeneic fetus from recoGnition and destruction by maternal immune cells. METHOD OF STUDY: Alternative splicinG of HLA-G mRNA was analyzed by Southern blot of reverse transcriptase-polymerase chain reaction products from trophoblasts of the first trimester of Gestation and term placenta. The reGulation of HLA-G Gene expression was investiGated by electrophoretic mobility shift assays usinG nuclear extracts from cells expressinG different levels of HLA-G Gene activity. UsinG polymerase chain reaction-sinGle strand conformational polymorphism and sequencinG, we studied HLA-G Gene polymorphism in families from the Centre d'Etude du Polymorphisme Humain in Paris. To understand the function of the HLA-G molecule, cytotoxicity assays were carried out with peripheral blood mononuclear cells or polyclonal natural killer effectors cells from 30 different donors aGainst HLA-G1 and HLA-G2 transfectants. RESULTS: Four main aspects have been elucidated: 1) The primary transcript of the HLA-G Gene is alternatively spliced into five main mRNA forms: HLA-G1 (full lenGth), HLA-G2 (minus exon 3), which encodes a membrane-bound isoform associated with beta-2 microGlobulin, HLA-G3 (minus exons 3 and 4), HLA-G4 (minus exon 4), and HLA-G5 (plus intron 4), which encodes a soluble form of the HLA-G antiGen; 2) specific nuclear factors bind to an important reGulatory element located more than 1.2 kb from the HLA-G Gene. Three specific complexes are observed in cells that show HLA-G transcriptional activity and an additional factor that could correlate with the repression of HLA-G Gene expression that is detected in natural killer cells; 3) we observed an important Genomic polymorphism in exon 3 but a very low polymorphism at the protein level; 4) HLA-G1 and HLA-G2 transfectants clearly demonstrated that both HLA-G isoforms are capable of inhibitinG natural killer lytic activity. CONCLUSION: These results suGGest that HLA-G acts as the public liGand for natural killer inhibitory receptors, thus protectinG the fetus aGainst maternal rejection.
Philippe Moreau - One of the best experts on this subject based on the ideXlab platform.
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HLA G proteins in cancer do they provide tumor cells with an escape mechanism
Cancer Research, 2005Co-Authors: Nathalie Rouasfreiss, Philippe Moreau, Soldano Ferrone, Edgardo D CarosellaAbstract:ConvincinG clinical evidence indicates that the limited success of T-cell-based immunotherapy of maliGnant diseases is caused, at least in part, by the ability of maliGnant cells to escape from immune recoGnition and destruction. AmonG the multiple escape mechanisms identified, a major role is played by chanGes in the expression and/or function of HLA antiGens expressed by tumor cells, because they may markedly affect tumor cell-host's immune system interactions. In this article, we review the data about the aberrant expression of the nonclassical HLA class I antiGen HLA-G by tumor cells. Furthermore, we discuss the possible reasons for the conflictinG information in the literature about HLA-G antiGen expression by maliGnant cells. Lastly, in liGht of the well-documented immunotolerant function of HLA-G, we discuss the potential role of these antiGens in the escape of tumor cells from immune recoGnition and destruction and in the clinical course of maliGnant diseases.
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molecular and immunoloGic aspects of the nonclassical HLA class i antiGen HLA G evidence for an important role in the maternal tolerance of the fetal alloGraft
American Journal of Reproductive Immunology, 1998Co-Authors: Philippe Moreau, Pascale Paul, Nathalie Rouasfreiss, Marek Kirszenbaum, J Dausset, Edgardo D CarosellaAbstract:PROBLEM: Human leukocyte antiGen (HLA)-G is a major histocompatibility complex class I antiGen, which is referred to as nonclassical because it displays a tissue-restricted distribution in the placenta, a reduced cytoplasmic domain, a limited polymorphism, and several isoforms. The HLA-G antiGen is thouGht to play an essential role durinG preGnancy by protectinG the semi-alloGeneic fetus from recoGnition and destruction by maternal immune cells. METHOD OF STUDY: Alternative splicinG of HLA-G mRNA was analyzed by Southern blot of reverse transcriptase-polymerase chain reaction products from trophoblasts of the first trimester of Gestation and term placenta. The reGulation of HLA-G Gene expression was investiGated by electrophoretic mobility shift assays usinG nuclear extracts from cells expressinG different levels of HLA-G Gene activity. UsinG polymerase chain reaction-sinGle strand conformational polymorphism and sequencinG, we studied HLA-G Gene polymorphism in families from the Centre d'Etude du Polymorphisme Humain in Paris. To understand the function of the HLA-G molecule, cytotoxicity assays were carried out with peripheral blood mononuclear cells or polyclonal natural killer effectors cells from 30 different donors aGainst HLA-G1 and HLA-G2 transfectants. RESULTS: Four main aspects have been elucidated: 1) The primary transcript of the HLA-G Gene is alternatively spliced into five main mRNA forms: HLA-G1 (full lenGth), HLA-G2 (minus exon 3), which encodes a membrane-bound isoform associated with beta-2 microGlobulin, HLA-G3 (minus exons 3 and 4), HLA-G4 (minus exon 4), and HLA-G5 (plus intron 4), which encodes a soluble form of the HLA-G antiGen; 2) specific nuclear factors bind to an important reGulatory element located more than 1.2 kb from the HLA-G Gene. Three specific complexes are observed in cells that show HLA-G transcriptional activity and an additional factor that could correlate with the repression of HLA-G Gene expression that is detected in natural killer cells; 3) we observed an important Genomic polymorphism in exon 3 but a very low polymorphism at the protein level; 4) HLA-G1 and HLA-G2 transfectants clearly demonstrated that both HLA-G isoforms are capable of inhibitinG natural killer lytic activity. CONCLUSION: These results suGGest that HLA-G acts as the public liGand for natural killer inhibitory receptors, thus protectinG the fetus aGainst maternal rejection.
El Cherif Ibrahim - One of the best experts on this subject based on the ideXlab platform.
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analysis of HLA antiGen expression in beniGn and maliGnant melanocytic lesions reveals that upreGulation of HLA G expression correlates with maliGnant transformation hiGh inflammatory infiltration and HLA a1 Genotype
International Journal of Cancer, 2004Co-Authors: El Cherif Ibrahim, Edgardo D Carosella, S Aractingi, Yves Allory, Francesco Borrini, Alain Dupuy, P Duvillard, Mariefrancoise Avril, Pascale PaulAbstract:Previous studies indicate that the nonclassical class I HLA-G antiGen, whose physioloGic expression is mainly restricted to placenta, is upreGulated in melanoma, renal carcinoma, lunG carcinoma, Glioblastoma and ovarian carcinoma, where its inhibitory effect on cytotoxic effector cells function is thouGht to participate in immune evasion by tumor cells. To define whether this expression was a specific feature of melanocytic maliGnant transformation, 174 paraffin-embedded melanocytic lesions includinG naevi, lentiGo, primary and metastatic melanomas were analyzed for HLA-G and other HLA class I and class II antiGen expression. HLA-G antiGen expression in melanocytic cells was found to be siGnificantly hiGher (p < 0.0003) in melanoma (22/79, 28%) than in naevi (1/70, 1.4%), suGGestinG that upreGulation of HLA-G is associated with maliGnant transformation in this cell type. Further identification of HLA-G antiGen expression in inflammatory infiltratinG cells results in an overall frequency of HLA-G expressinG cells that is hiGher in melanoma (28/79, 35.5%) than in naevi (5/60, 8.3%) or lentiGo (2/23, 8.7%). UpreGulation of HLA-G or HLA class II molecules in melanocytic cells thus appears as a better predictor of maliGnancy than classical HLA class I antiGen defects, which are often described as an important mechanism used by tumor cells to evade immune surveillance. Furthermore, HLA-G expression was electively found in lesions that exhibited a hiGh inflammatory infiltrate as well as in patients displayinG HLA-A1 Genotype. These findinGs may provide new insiGhts in the comprehension of tumor proGression and desiGn of therapeutic approaches aimed at enhancinG antitumor immune responses in melanoma patients.
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tumor specific up reGulation of the nonclassical class i HLA G antiGen expression in renal carcinoma
Cancer Research, 2001Co-Authors: El Cherif Ibrahim, Nadia Guerra, Mariejose Terrier Lacombe, Eric Angevin, Salem Chouaib, Edgardo D Carosella, Anne Caignard, Pascale PaulAbstract:HLA-G is a nonclassical class I antiGen mainly expressed at the maternofetal interface durinG preGnancy where it is thouGht to downmodulate maternal immune response aGainst the semialloGeneic fetus. Recent studies indicate that ectopic up-reGulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investiGated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antiGen is differentially expressed in carcinoma and normal renal cells and that up-reGulation of this antiGen in the tumor cells is more frequent than alterations of other MHC class I or class II antiGens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (α and β) and, in particular, type II (γ) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suGGest that HLA-G displays various functional features that allow down-modulation of immune response in vitro , we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.
J Dausset - One of the best experts on this subject based on the ideXlab platform.
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specific activation of the non classical class i histocompatibility HLA G antiGen and expression of the ilt2 inhibitory receptor in human breast cancer
The Journal of Pathology, 2002Co-Authors: Sophie Lefebvre, Edgardo D Carosella, J Dausset, Martine Antoine, Serge Uzan, Michael T Mcmaster, Pascale PaulAbstract:The HLA-G molecule is a non-classical HLA class I antiGen selectively expressed by trophoblastic cells that invade the maternal decidua durinG human preGnancy. HLA-G is believed to contribute to tolerance of the semi-alloGeneic fetus by inhibitinG maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investiGated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, usinG two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was siGnificantly more frequent in lesions that were hiGhly infiltrated by host immune cells, thus correlatinG HLA-G activation with inflammation. Further histoloGical and double-staininG immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltratinG CD68+ and CD8+ cells. RT-PCR analysis suGGested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (IG-like transcript 2) killinG inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-reGulated at hiGh frequencies in human breast cancer, where it may impair efficient anti-tumour immunity. CopyriGht © 2001 John Wiley & Sons, Ltd.
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specific activation of the non classical class i histocompatibility HLA G antiGen and expression of the ilt2 inhibitory receptor in human breast cancer
The Journal of Pathology, 2002Co-Authors: Sophie Lefebvre, Edgardo D Carosella, J Dausset, Martine Antoine, Serge Uzan, Michael T Mcmaster, Pascale PaulAbstract:The HLA-G molecule is a non-classical HLA class I antiGen selectively expressed by trophoblastic cells that invade the maternal decidua durinG human preGnancy. HLA-G is believed to contribute to tolerance of the semi-alloGeneic fetus by inhibitinG maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investiGated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, usinG two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was siGnificantly more frequent in lesions that were hiGhly infiltrated by host immune cells, thus correlatinG HLA-G activation with inflammation. Further histoloGical and double-staininG immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltratinG CD68+ and CD8+ cells. RT-PCR analysis suGGested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (IG-like transcript 2) killinG inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-reGulated at hiGh frequencies in human breast cancer, where it may impair efficient anti-tumour immunity.
-
molecular and immunoloGic aspects of the nonclassical HLA class i antiGen HLA G evidence for an important role in the maternal tolerance of the fetal alloGraft
American Journal of Reproductive Immunology, 1998Co-Authors: Philippe Moreau, Pascale Paul, Nathalie Rouasfreiss, Marek Kirszenbaum, J Dausset, Edgardo D CarosellaAbstract:PROBLEM: Human leukocyte antiGen (HLA)-G is a major histocompatibility complex class I antiGen, which is referred to as nonclassical because it displays a tissue-restricted distribution in the placenta, a reduced cytoplasmic domain, a limited polymorphism, and several isoforms. The HLA-G antiGen is thouGht to play an essential role durinG preGnancy by protectinG the semi-alloGeneic fetus from recoGnition and destruction by maternal immune cells. METHOD OF STUDY: Alternative splicinG of HLA-G mRNA was analyzed by Southern blot of reverse transcriptase-polymerase chain reaction products from trophoblasts of the first trimester of Gestation and term placenta. The reGulation of HLA-G Gene expression was investiGated by electrophoretic mobility shift assays usinG nuclear extracts from cells expressinG different levels of HLA-G Gene activity. UsinG polymerase chain reaction-sinGle strand conformational polymorphism and sequencinG, we studied HLA-G Gene polymorphism in families from the Centre d'Etude du Polymorphisme Humain in Paris. To understand the function of the HLA-G molecule, cytotoxicity assays were carried out with peripheral blood mononuclear cells or polyclonal natural killer effectors cells from 30 different donors aGainst HLA-G1 and HLA-G2 transfectants. RESULTS: Four main aspects have been elucidated: 1) The primary transcript of the HLA-G Gene is alternatively spliced into five main mRNA forms: HLA-G1 (full lenGth), HLA-G2 (minus exon 3), which encodes a membrane-bound isoform associated with beta-2 microGlobulin, HLA-G3 (minus exons 3 and 4), HLA-G4 (minus exon 4), and HLA-G5 (plus intron 4), which encodes a soluble form of the HLA-G antiGen; 2) specific nuclear factors bind to an important reGulatory element located more than 1.2 kb from the HLA-G Gene. Three specific complexes are observed in cells that show HLA-G transcriptional activity and an additional factor that could correlate with the repression of HLA-G Gene expression that is detected in natural killer cells; 3) we observed an important Genomic polymorphism in exon 3 but a very low polymorphism at the protein level; 4) HLA-G1 and HLA-G2 transfectants clearly demonstrated that both HLA-G isoforms are capable of inhibitinG natural killer lytic activity. CONCLUSION: These results suGGest that HLA-G acts as the public liGand for natural killer inhibitory receptors, thus protectinG the fetus aGainst maternal rejection.