The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Francisco Ruiz-cabello - One of the best experts on this subject based on the ideXlab platform.
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Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with Tumor microsatellite instability but not with Tumor Immunogenicity
Cancer Immunology Immunotherapy, 2011Co-Authors: Mónica Bernal, Ángel Concha, Pablo Sáenz-lópez, Ana I. Rodriguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-cabelloAbstract:Purpose To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with Tumor Immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression. Experimental design Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadic high-level microsatellite instability (MSI-H) or microsatellite stability (MSS). Results Tumors with MSI-H were associated with the following: dense infiltration (CD45, P
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Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with Tumor microsatellite instability but not with Tumor Immunogenicity
Cancer immunology immunotherapy : CII, 2011Co-Authors: Mónica Bernal, Ángel Concha, Pablo Sáenz-lópez, Ana I. Rodriguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-cabelloAbstract:Purpose To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with Tumor Immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression.
Thomas B. Tomasi - One of the best experts on this subject based on the ideXlab platform.
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The modulation of Dicer regulates Tumor Immunogenicity in melanoma
Oncotarget, 2016Co-Authors: Nicholas C. Hoffend, William J. Magner, Thomas B. TomasiAbstract:// Nicholas C. Hoffend 1 , William J. Magner 1, 3 , Thomas B. Tomasi 1, 2, 3 1 Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA 2 Department of Medicine, State University of New York, Buffalo, New York, USA 3 Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York, USA Correspondence to: Thomas B. Tomasi, email: Thomas.Tomasi@roswellpark.org Keywords: Dicer, microRNA, melanoma, Immunogenicity, CD8 + T cells Received: February 02, 2016 Accepted: June 12, 2016 Published: June 23, 2016 ABSTRACT MicroRNAs (miRs) are small non-coding RNAs that regulate most cellular protein networks by targeting mRNAs for translational inhibition or degradation. Dicer, a type III endoribonuclease, is a critical component in microRNA biogenesis and is required for mature microRNA production. Abnormal Dicer expression occurs in numerous cancer types and correlates with poor patient prognosis. For example, increased Dicer expression in melanoma is associated with more aggressive Tumors (higher Tumor mitotic index and depth of invasion) and poor patient prognosis. However, the role that Dicer plays in melanoma development and immune evasion remains unclear. Here, we report on a newly discovered relationship between Dicer expression and Tumor Immunogenicity. To investigate Dicer’s role in regulating melanoma Immunogenicity, Dicer knockdown studies were performed. We found that B16F0-Dicer deficient cells exhibited decreased Tumor growth compared to control cells and were capable of inducing anti-Tumor immunity. The decrease in Tumor growth was abrogated in immunodeficient NSG mice and was shown to be dependent upon CD8 + T cells. Dicer knockdown also induced a more responsive immune gene profile in melanoma cells. Further studies demonstrated that CD8 + T cells preferentially killed Dicer knockdown Tumor cells compared to control cells. Taken together, we present evidence which links Dicer expression to Tumor Immunogenicity in melanoma.
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Dicer regulates Tumor Immunogenicity in melanoma
Journal of Immunology, 2016Co-Authors: Nicholas C. Hoffend, William J. Magner, Thomas B. TomasiAbstract:Immunotherapeutic strategies in cancer rely upon Tumor Immunogenicity for their efficacy. However, the regulation of immune effector molecules in melanoma is poorly understood. High Dicer expression in melanoma correlates with more aggressive Tumors and poor prognosis/patient survival. Dicer regulates gene expression through processing of microRNAs, but its potential role in regulating the Immunogenicity of melanoma has not been described. Here, we demonstrate that Dicer suppresses MHC class I and II cell surface expression, as well as CD40 and PD-L1 in melanoma. By using a genetic approach wherein we challenged C57BL/6 mice with melanoma cells stably expressing Dicer shRNA, we showed that Dicer knockdown decreased Tumor progression and extended overall survival. Interestingly, Dicer knockdown had no effect on melanoma cell proliferation or survival in vitro , suggesting that the delay in Tumor growth may be due to an augmented immune response. Tumor control of Dicer knockdown melanoma cells was dependent upon an intact immune system, as revealed by studies using NSG mice. Mechanistically, this anti-Tumor immune response was dependent upon CD8 + T cells. Subsequent studies demonstrated that melanoma Dicer expression was able to suppress CD8 + T cell killing in vitro . Taken together, this suggests a model wherein Dicer negatively regulates melanoma Immunogenicity and protects against CD8 + T cell anti-Tumor immunity. Using this insight, we may better stratify patients for immunotherapies such as checkpoint inhibition and cell-based vaccination strategies. Dicer also makes an attractive target for modulating baseline Tumor cell Immunogenicity, subsequently enhancing melanoma immunotherapy and patient survival.
Salem Chouaib - One of the best experts on this subject based on the ideXlab platform.
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Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity.
International Journal of Molecular Sciences, 2018Co-Authors: Stéphane Terry, Rania Faouzi Zaarour, Goutham Hassan Venkatesh, Amirtharaj Francis, Walid El-sayed, Stéphanie Buart, Pamela Bravo, Jerome Thiery, Salem ChouaibAbstract:Hypoxia, or gradients of hypoxia, occurs in most growing solid Tumors and may result in pleotropic effects contributing significantly to Tumor aggressiveness and therapy resistance. Indeed, the generated hypoxic stress has a strong impact on Tumor cell biology. For example, it may contribute to increasing Tumor heterogeneity, help cells gain new functional properties and/or select certain cell subpopulations, facilitating the emergence of therapeutic resistant cancer clones, including cancer stem cells coincident with Tumor relapse and progression. It controls Tumor Immunogenicity, immune plasticity, and promotes the differentiation and expansion of immune-suppressive stromal cells. In this context, manipulation of the hypoxic microenvironment may be considered for preventing or reverting the malignant transformation. Here, we review the current knowledge on how hypoxic stress in Tumor microenvironments impacts on Tumor heterogeneity, plasticity and resistance, with a special interest in the impact on immune resistance and Tumor Immunogenicity.
Federico Garrido - One of the best experts on this subject based on the ideXlab platform.
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Targeting HLA class I expression to increase Tumor Immunogenicity
Tissue antigens, 2012Co-Authors: A. B. Del Campo, Javier Carretero, Natalia Aptsiauri, Federico GarridoAbstract:The dynamic interaction between the host immune system and growing cancer has been of central interest to the field of Tumor immunology over the past years. Recognition of Tumor-associated antigens (TAA) by self-HLA (human leukocyte antigen) class I-restricted CD8+ T cells is a main feature in the detection and destruction of malignant cells. The discovery and molecular characterization of TAA has changed the field of cancer treatment and introduced a new era of cancer immunotherapy aimed at increasing Tumor Immunogenicity and T-cell-mediated anti-Tumor immunity. Unfortunately, while these new protocols of cancer immunotherapy are mediating induction of Tumor-specific T lymphocytes in patients with certain malignancies, they have not yet delivered substantial clinical benefits, such as induction of Tumor regression or increased disease-free survival. It has become apparent that lack of Tumor rejection is the result of immune selection and escape by Tumor cells that develop low immunogenic phenotypes. Substantial experimental data support the existence of a variety of different mechanisms involved in the Tumor escape phase, including loss or downregulation of HLA class I antigens. These alterations could be caused by regulatory (‘soft’) or by structural/irreversible (‘hard’) defects. On the basis of the evidence obtained from experimental mouse cancer models and metastatic human Tumors, the structural defects underlying HLA class I loss may have profound implications on T-cell-mediated Tumor rejection and ultimately on the outcome of cancer immunotherapy. Strategies to overcome this obstacle, including gene therapy to recover normal expression of HLA class I genes, require consideration. In this review, we outline the importance of monitoring and correction of HLA class I alterations during cancer development and immunotherapy.
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Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with Tumor microsatellite instability but not with Tumor Immunogenicity
Cancer Immunology Immunotherapy, 2011Co-Authors: Mónica Bernal, Ángel Concha, Pablo Sáenz-lópez, Ana I. Rodriguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-cabelloAbstract:Purpose To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with Tumor Immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression. Experimental design Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadic high-level microsatellite instability (MSI-H) or microsatellite stability (MSS). Results Tumors with MSI-H were associated with the following: dense infiltration (CD45, P
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Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with Tumor microsatellite instability but not with Tumor Immunogenicity
Cancer immunology immunotherapy : CII, 2011Co-Authors: Mónica Bernal, Ángel Concha, Pablo Sáenz-lópez, Ana I. Rodriguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-cabelloAbstract:Purpose To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with Tumor Immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression.
Mónica Bernal - One of the best experts on this subject based on the ideXlab platform.
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Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with Tumor microsatellite instability but not with Tumor Immunogenicity
Cancer Immunology Immunotherapy, 2011Co-Authors: Mónica Bernal, Ángel Concha, Pablo Sáenz-lópez, Ana I. Rodriguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-cabelloAbstract:Purpose To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with Tumor Immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression. Experimental design Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadic high-level microsatellite instability (MSI-H) or microsatellite stability (MSS). Results Tumors with MSI-H were associated with the following: dense infiltration (CD45, P
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Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with Tumor microsatellite instability but not with Tumor Immunogenicity
Cancer immunology immunotherapy : CII, 2011Co-Authors: Mónica Bernal, Ángel Concha, Pablo Sáenz-lópez, Ana I. Rodriguez, Teresa Cabrera, Federico Garrido, Francisco Ruiz-cabelloAbstract:Purpose To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with Tumor Immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression.
