Targeted Disruption of Tumor-Derived Chemokine Synthesis and Reversal of Tumor-Induced Immune Suppression PDF Download
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Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 29
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Book Description
Chemokines play a pivotal role in the maturation of the immune system, and in the initiation, and maintenance of an immune response. Because of their key role in the immune response, the aberrant expression of chemokines can have a profound effect on the ability of T cells to respond to antigen. We have found that several breast cancer cell lines produced chemokines capable of recruiting T cells. However, instead of increasing anti-tumor immunity, the tumor-derived chemokines may have prevented an effective immune response by desensitizing T-cell chemokine receptors. Our hypothesis is that disrupting the synthesis of tumor-derived chemokines (using anti-sense technology) will remove tumor- induced immune suppression and enhance the immunogenicity of the tumor. In order to test this hypothesis we generated stable clones that lack CCL2 and CCL5 production compared to the parental tumor cell line. Using these tumors we found that both CCL2 and CCL5 impair the T cell response to the murine mammary carcinoma 4Tl. Moreover, tumor-derived CCL5 impaired T cell chemotactic activity and enhanced growth of the tumor in vivo. In addition, we found that tumor- derived CXCL 1 acts as an autocrine growth factor and angiogenesis factor for 4T 1.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 29
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Book Description
Chemokines play a pivotal role in the maturation of the immune system, and in the initiation, and maintenance of an immune response. Because of their key role in the immune response, the aberrant expression of chemokines can have a profound effect on the ability of T cells to respond to antigen. We have found that several breast cancer cell lines produced chemokines capable of recruiting T cells. However, instead of increasing anti-tumor immunity, the tumor-derived chemokines may have prevented an effective immune response by desensitizing T-cell chemokine receptors. Our hypothesis is that disrupting the synthesis of tumor-derived chemokines (using anti-sense technology) will remove tumor- induced immune suppression and enhance the immunogenicity of the tumor. In order to test this hypothesis we generated stable clones that lack CCL2 and CCL5 production compared to the parental tumor cell line. Using these tumors we found that both CCL2 and CCL5 impair the T cell response to the murine mammary carcinoma 4Tl. Moreover, tumor-derived CCL5 impaired T cell chemotactic activity and enhanced growth of the tumor in vivo. In addition, we found that tumor- derived CXCL 1 acts as an autocrine growth factor and angiogenesis factor for 4T 1.
Author: Dmitry I. Gabrilovich
Publisher: Springer Science & Business Media
ISBN: 0387691189
Category : Medical
Languages : en
Pages : 304
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Book Description
This monograph, for the first time, presents a comprehensive overview of different mechanisms of immune dysfunction in cancer as well as therapeutic approaches to their correction. It discusses a number of new mechanisms that have never been discussed in a monograph before: T-cell inhibitory molecules, regulatory tolerogenic DCs, and signaling pathways in antigen-presenting cells involved in T-cell tolerance. There is now a pressing need to discuss the already described and newly emerging mechanisms to see how they can be put together in a more or less cohesive structure and how they can help to improve immune response to tumors.
Author: Dmitry I. Gabrilovich
Publisher: Springer Science & Business Media
ISBN: 1489980563
Category : Medical
Languages : en
Pages : 471
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Book Description
Tumor-Induced Immune Suppression - Prospects and Progress in Mechanisms and Therapeutic Reversal presents a comprehensive overview of large number of different mechanisms of immune dysfunction in cancer and therapeutic approaches to their correction. This includes the number of novel mechanisms that has never before been discussed in previous monographs. The last decades were characterized by substantial progress in the understanding of the role of the immune system in tumor progression. Researchers have learned how to manipulate the immune system to generate tumor specific immune response, which raises high expectations for immunotherapy to provide breakthroughs in cancer treatment. It is increasingly clear that tumor-induced abnormalities in the immune system not only hampers natural tumor immune surveillance, but also limits the effect of cancer immunotherapy. Therefore, it is critically important to understand the mechanisms of tumor-induced immune suppression to make any progress in the field and this monograph provides these important insights.
Author: Marie-Caroline Dieu-Nosjean
Publisher: Humana Press
ISBN: 9781493987085
Category : Medical
Languages : en
Pages : 289
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Book Description
This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.
Author: Bharat B. Aggarwal
Publisher: Springer
ISBN: 3034808372
Category : Medical
Languages : en
Pages : 489
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Book Description
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Author: R. John Bicknell
Publisher:
ISBN:
Category : Neovascularization
Languages : en
Pages : 416
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Book Description
Tumour Angiogenesis is the first comprehensive book to cover all areas of this rapidly expanding research area. Each chapter is written by world experts in the field and topics covered include in vivo models, mechanisms, inhibition, and the role of macrophages, cytokines, proteases,extracellular matrix components, nitric oxide, prostanoids and oncogenes/tumour suppressor genes in angiogenesis. Other chapters examine the role of specific growth factors in angiogenesis - these include vascular endothelial growth factor, the basic fibroblast growth factor family, transforminggrowth factor-beta, tumour necrosis factor-alpha, platelet-derived endothelial cell growth factor/thymidine phosphorylase and pleiotrophin and related molecules. Clinical issues are addressed in chapters that deal with the prognostic and predictive value of tumour microvessel density and thetherapeutic significance of microregional blood flow. The two final chapters examine the feasibility of targeting tumour vasculature using either antibodies or gene therapy.
Author: Adriano Rossi
Publisher: Springer Science & Business Media
ISBN: 376437506X
Category : Medical
Languages : en
Pages : 246
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Book Description
This book provides readers with an up-to-date and comprehensive view on the resolution of inflammation and on new developments in this area, including pro-resolution mediators, apoptosis, macrophage clearance of apoptotic cells, possible novel drug developments.
Author: Jamie A. Goode
Publisher: John Wiley & Sons
ISBN: 9780471499596
Category : Science
Languages : en
Pages : 322
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Book Description
Ergebnisse von in vitro-Studien lassen vermuten, dass sich der pH-Wert in einem Tumor auf die Wirksamkeit von Chemo- oder Strahlentherapien auswirken kann. Wie aber sieht die Beziehung zwischen der Tumorentwicklung und dem pH-Wert aus? Können ein niedriger pH-Wert oder ein Sauerstoffmangel die Carcinogenese hemmen? Wo bieten sich therapeutische Ansätze? Anwort auf diese und andere Fragen finden Sie in diesem Band. In interdisziplinärer Weise wurden Beiträge aus der Grundlagenforschung und der klinischen Praxis zusammengetragen.
Author: Thorsten Cramer
Publisher: Springer
ISBN: 3319421182
Category : Medical
Languages : en
Pages : 272
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Book Description
This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.
Author: Herbert Levine
Publisher: Academic Press
ISBN: 012817997X
Category : Medical
Languages : en
Pages : 773
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Book Description
Phenotypic Switching: Implications in Biology and Medicine provides a comprehensive examination of phenotypic switching across biological systems, including underlying mechanisms, evolutionary significance, and its role in biomedical science. Contributions from international leaders discuss conceptual and theoretical aspects of phenotypic plasticity, its influence over biological development, differentiation, biodiversity, and potential applications in cancer therapy, regenerative medicine and stem cell therapy, among other treatments. Chapters discuss fundamental mechanisms of phenotypic switching, including transition states, cell fate decisions, epigenetic factors, stochasticity, protein-based inheritance, specific areas of human development and disease relevance, phenotypic plasticity in melanoma, prostate cancer, breast cancer, non-genetic heterogeneity in cancer, hepatitis C, and more. This book is essential for active researchers, basic and translational scientists, clinicians, postgraduates and students in genetics, human genomics, pathology, bioinformatics, developmental biology, evolutionary biology and adaptive opportunities in yeast. Thoroughly addresses the conceptual, experimental and translational aspects that underlie phenotypic plasticity Emphasizes quantitative approaches, nonlinear dynamics, mechanistic insights and key methodologies to advance phenotypic plasticity studies Features a diverse range of chapter contributions from international leaders in the field
