The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Soldano Ferrone - One of the best experts on this subject based on the ideXlab platform.
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the hdac inhibitor domatinostat promotes cell cycle arrest induces apoptosis and increases immunogenicity of merkel cell carcinoma cells
Journal of Investigative Dermatology, 2021Co-Authors: Lina Song, Soldano Ferrone, Anne Catherine Bretz, Jan Gravemeyer, Ivelina Spassova, Shakhlo Muminova, T Gambichler, Ashwin Sriram, Jurgen C BeckerAbstract:Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer for which immune modulation by immune checkpoint inhibitors shows remarkable response rates. However, primary or secondary resistance to immunotherapy prevents benefits in a significant proportion of patients. For MCC, one immune escape mechanism is insufficient for recognition by T cells owing to the downregulation of major histocompatibility complex I surface expression. Histone deacetylase inhibitors have been demonstrated to epigenetically reverse the low major histocompatibility complex I expression caused by the downregulation of the antigen-processing Machinery. Domatinostat, an orally available small-molecule inhibitor targeting histone deacetylase class I, is currently in clinical evaluation to overcome resistance to immunotherapy. In this study, we present preclinical data on domatinostat's efficacy and mode of action in MCC. Single-cell RNA sequencing revealed a distinct gene expression signature of antigen processing and presentation, cell-cycle arrest, and execution phase of apoptosis on treatment. Accordingly, functional assays showed that domatinostat induced G2M arrest and apoptosis. In the surviving cells, antigen-processing Machinery Component gene transcription and translation were upregulated, consequently resulting in increased major histocompatibility complex I surface expression. Altogether, domatinostat not only exerts direct antitumoral effects but also restores HLA class I surface expression on MCC cells, therefore, restoring surviving MCC cells' susceptibility to recognition and elimination by cognate cytotoxic T cells.
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Abstract Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p<0.05); their levels were significantly high in SLN LCs (p<0.01). APM Component expression correlated with melanoma Breslow's thickness and SLN metastases: HLA-A,B,C level was significantly lower in SLN LCs from thick lesions patients compared with those from thin/intermediate lesions (p<0.05); β2-microglobulin level was significantly higher in positive SLN LCs compared to negative ones (p<0.05). Functionally, SLN LCs did not phagocytose exogenous antigens. These findings extend LCs knowledge indicating that they are not fully impaired by melanoma, contributing to design new LCs-based therapeutic approaches.
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immunological and clinical significance of hla class i antigen processing Machinery Component defects in malignant cells
Oral Oncology, 2016Co-Authors: Fernando Conchabenavente, Soldano Ferrone, Raghvendra M Srivastava, Robert L FerrisAbstract:Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes. Two major mechanisms, which affect the target cells and the effector phase of the immune response, play a crucial role in the editing process. One is represented by the downregulation of tumor antigen (TA) processing and presentation because of abnormalities in the HLA class I antigen processing Machinery (APM). The other one is represented by the anergy of effector immune infiltrates in the tumor microenvironment caused by aberrant inhibitory signals triggered by immune checkpoint receptor (ICR) ligands, such as programmed death ligand-1 (PD-L1). In this review, we will focus on tumor immune escape mechanisms caused by defects in HLA class I APM Component expression and/or function in different types of cancer, with emphasis on head and neck cancer (HNC). We will also discuss the immunological implications and clinical relevance of these HLA class I APM abnormalities. Finally, we will describe strategies to counteract defective TA presentation with the expectation that they will enhance tumor recognition and elimination by tumor infiltrating effector T cells.
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mhc class i related antigen processing Machinery Component defects in feline mammary carcinoma
Translational Oncology, 2012Co-Authors: Alessandra Favole, Soldano Ferrone, Paolo Cascio, Fulvia Cerruti, Alessandra Sereno, Massimiliano Tursi, Alessandro Tomatis, Cristina Della Beffa, Enrico BolloAbstract:Defects in HLA class I antigen-processing Machinery (APM) Component expression and/or function are frequent in human tumors. These defects may provide tumor cells with a mechanism to escape from recognition and destruction by HLA class I antigen-restricted, tumor antigen-specific cytotoxic T cells. However, expression and functional properties of MHC class I antigens and APM Components in malignant cells in other animal species have been investigated to a limited extent. However, this information can contribute to our understanding of the mechanisms underlying the association of MHC class I antigen and APM Component defects with malignant transformation of cells and to identify animal models to validate targeted therapies to correct these defects. To overcome this limitation in the present study, we have investigated the expression of the catalytic subunits of proteasome (Y, X, and Z) and of immunoproteasome (LMP2, LMP7, and LMP10) as well as of MHC class I heavy chain (HC) in 25 primary feline mammary carcinomas (FMCs) and in 23 matched healthy mammary tissues. We found a reduced expression of MHC class I HC and of LMP2 and LMP7 in tumors compared with normal tissues. Concordantly, proteasomal cleavage specificities in extracts from FMCs were different from those in healthy tissues. In addition, correlation analysis showed that LMP2 and LMP7 were concordantly expressed in FMCs, and their expression was significantly correlated with that of MHC class I HC. The abnormalities we have found in the APM in FMCs may cause a defective processing of some tumor antigens.
Lorenzo Borgognoni - One of the best experts on this subject based on the ideXlab platform.
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Abstract Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p<0.05); their levels were significantly high in SLN LCs (p<0.01). APM Component expression correlated with melanoma Breslow's thickness and SLN metastases: HLA-A,B,C level was significantly lower in SLN LCs from thick lesions patients compared with those from thin/intermediate lesions (p<0.05); β2-microglobulin level was significantly higher in positive SLN LCs compared to negative ones (p<0.05). Functionally, SLN LCs did not phagocytose exogenous antigens. These findings extend LCs knowledge indicating that they are not fully impaired by melanoma, contributing to design new LCs-based therapeutic approaches.
Maria Raffaella Romoli - One of the best experts on this subject based on the ideXlab platform.
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Abstract Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p<0.05); their levels were significantly high in SLN LCs (p<0.01). APM Component expression correlated with melanoma Breslow's thickness and SLN metastases: HLA-A,B,C level was significantly lower in SLN LCs from thick lesions patients compared with those from thin/intermediate lesions (p<0.05); β2-microglobulin level was significantly higher in positive SLN LCs compared to negative ones (p<0.05). Functionally, SLN LCs did not phagocytose exogenous antigens. These findings extend LCs knowledge indicating that they are not fully impaired by melanoma, contributing to design new LCs-based therapeutic approaches.
Paola Di Gennaro - One of the best experts on this subject based on the ideXlab platform.
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Abstract Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p<0.05); their levels were significantly high in SLN LCs (p<0.01). APM Component expression correlated with melanoma Breslow's thickness and SLN metastases: HLA-A,B,C level was significantly lower in SLN LCs from thick lesions patients compared with those from thin/intermediate lesions (p<0.05); β2-microglobulin level was significantly higher in positive SLN LCs compared to negative ones (p<0.05). Functionally, SLN LCs did not phagocytose exogenous antigens. These findings extend LCs knowledge indicating that they are not fully impaired by melanoma, contributing to design new LCs-based therapeutic approaches.
Paola Brandani - One of the best experts on this subject based on the ideXlab platform.
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Abstract Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p
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high antigen processing Machinery Component expression in langerhans cells from melanoma patients sentinel lymph nodes
Cellular Immunology, 2017Co-Authors: Maria Raffaella Romoli, Soldano Ferrone, Paola Di Gennaro, Gianni Gerlini, Serena Sestini, Paola Brandani, Lorenzo BorgognoniAbstract:Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM Components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM Component levels were low in immature epidermal LCs and significantly increased after maturation (p<0.05); their levels were significantly high in SLN LCs (p<0.01). APM Component expression correlated with melanoma Breslow's thickness and SLN metastases: HLA-A,B,C level was significantly lower in SLN LCs from thick lesions patients compared with those from thin/intermediate lesions (p<0.05); β2-microglobulin level was significantly higher in positive SLN LCs compared to negative ones (p<0.05). Functionally, SLN LCs did not phagocytose exogenous antigens. These findings extend LCs knowledge indicating that they are not fully impaired by melanoma, contributing to design new LCs-based therapeutic approaches.
