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Tumor-Induced Immune Suppression

Tumor-Induced Immune Suppression
Author: Dmitry I. Gabrilovich
Publisher: Springer Science & Business Media
Total Pages: 471
Release: 2014-02-10
Genre: Medical
ISBN: 1489980563

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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.


Tumor-Induced Immune Suppression

Tumor-Induced Immune Suppression
Author: Dmitry I. Gabrilovich
Publisher: Springer Science & Business Media
Total Pages: 304
Release: 2008-01-01
Genre: Medical
ISBN: 0387691189

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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.


Tumor Induced Immune Suppression

Tumor Induced Immune Suppression
Author: Craig Anthony Mullen
Publisher:
Total Pages: 244
Release: 1984
Genre: Immunosuppression
ISBN:

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Cancer Immunotherapy

Cancer Immunotherapy
Author: Suzanne Ostrand-Rosenberg
Publisher: Elsevier Inc. Chapters
Total Pages: 50
Release: 2013-06-04
Genre: Medical
ISBN: 0128059249

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Immune escape and inflammation are now recognized as hallmarks of tumor onset and progression. Myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells that are present in virtually all patients and mice with advanced cancer, are a major contributor to immune escape through their inhibition of innate and adaptive antitumor immunity. Immature myeloid cells with the phenotype of MDSC are present in low levels in healthy individuals; however, chronic inflammation perturbs normal myelopoiesis and mobilizes MDSC, thereby facilitating tumor growth. This chapter reviews the experimental and patient findings that identified MDSC as an immune suppressive cell population mediating tumor immune escape, the phenotypic characteristics and heterogeneity of MDSC from cancer patients and mice, the diversity of mechanisms used by MDSC to facilitate tumor progression and metastasis, the pro-inflammatory mediators that drive the induction and accumulation of MDSC, and therapeutic approaches that have been developed to reduce MDSC levels and/or impair MDSC function.


Cancer Immunotherapy

Cancer Immunotherapy
Author: George C. Prendergast
Publisher: Academic Press
Total Pages: 679
Release: 2013-06-04
Genre: Medical
ISBN: 0123946336

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There has been major growth in understanding immune suppression mechanisms and its relationship to cancer progression and therapy. This book highlights emerging new principles of immune suppression that drive cancer, and it offers radically new ideas about how therapy can be improved by attacking these principles. Following work that firmly establishes immune escape as an essential trait of cancer, recent studies have now defined specific mechanisms of tumor immune suppression. It also demonstrates how attacking tumors with molecular targeted therapeutics or traditional chemotherapeutic drugs can produce potent anti-tumor effects in preclinical models. This book provides basic, translational, and clinical cancer researchers with an indispensable overview of immune escape as a critical trait in cancer and how applying specific combinations of immunotherapy and chemotherapy to attack this trait may radically improve the treatment of advanced disease. Offers a synthesis of concepts that are useful to cancer immunologists and pharmacologists, who tend to work in disparate fields with little cross-communication Drs. Prendergast and Jaffee are internationally recognized leaders in cancer biology and immunology who have created a unique synthesis of fundamental and applied concepts in this important new area of cancer research Summarizes the latest insights into how immune escape defines an essential trait of cancer Includes numerous illustrations, including how molecular-targeted therapeutic drugs or traditional chemotherapy can be combined with immunotherapy to improve anti-tumor efficacy and how reversing immune suppression by the tumor can cause tumor regression


Tertiary Lymphoid Structures

Tertiary Lymphoid Structures
Author: Marie-Caroline Dieu-Nosjean
Publisher: Humana Press
Total Pages: 289
Release: 2018-09-05
Genre: Medical
ISBN: 9781493987085

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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.


Cancer Immunotherapy at the Crossroads

Cancer Immunotherapy at the Crossroads
Author: James H. Finke
Publisher: Springer Science & Business Media
Total Pages: 392
Release: 2003-11-24
Genre: Medical
ISBN: 1592597432

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Leading investigators and clinicians detail the different mechanisms used by tumors to escape and impair the immune system and then spell out possible clinical strategies to prevent or reverse tumor-induced immune dysfunction. The authors review the mechanisms of immune dysfunction and evasion mechanisms in histologically diverse human tumors, focusing on tumor-induced molecular defects in T cells and antigen-presenting cells (dendritic cells and tumors), that may serve as biomarkers for patient prognosis. They discuss the means by which these immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques are outlined with the capacity to monitor the strength and quality of patients' immune responses using immunocytometry, MHC-peptide tetramers combined with apoptosis assay, ELISPOT assay, and detection of MHC-TAA peptide complexes on tumor cells.


Targeted Disruption of Tumor-Derived Chemokine Synthesis and Reversal of Tumor-Induced Immune Suppression

Targeted Disruption of Tumor-Derived Chemokine Synthesis and Reversal of Tumor-Induced Immune Suppression
Author:
Publisher:
Total Pages: 14
Release: 2002
Genre:
ISBN:

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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 have generated stable clones that lack MCP-l and RANTES production compared to the parental tumor cell line. Using these tumors we will determine whether the T cells are better able to elicit an anti-tumor immune response by comparing the immunogenicity of the tumors that do and do not express chemokines. These tumor cells will be evaluated by immunization/challenge experiments and by the ability to generate tumor-specific T cells in vaccine draining lymph nodes.


Cancer Immunotherapy

Cancer Immunotherapy
Author: David H. Munn
Publisher: Elsevier Inc. Chapters
Total Pages: 31
Release: 2013-06-04
Genre: Medical
ISBN: 012805929X

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Indoleamine 2,3-dioxygenase (IDO) is a metabolic pathway implicated in a number of settings that lead to acquired peripheral tolerance. IDO may also participate in the functional tolerance of the immune system towards tumors. Foxp3+ Tregs are major contributors to tumor-induced immune suppression, and emerging evidence links the IDO pathway with Treg activation. IDO-expressing dendritic cells (DCs) can drive the differentiation of naive CD4+ T cells into Foxp3+ Tregs. IDO+ DCs can also directly activate mature, preformed Tregs to mediate enhanced suppression. In experimental models, IDO also stabilizes the suppressive Treg phenotype and prevents inflammation-induced reprogramming of Tregs into pro-inflammatory (T-helper-like) cells. IDO may thus represent an important regulatory checkpoint that enhances Treg activity in tumor-bearing hosts. Drugs that target the IDO pathway may assist in reducing Treg-mediated suppression during antitumor immunotherapy.


Mechanisms of Tumor Escape from the Immune Response

Mechanisms of Tumor Escape from the Immune Response
Author: A Ochoa
Publisher: CRC Press
Total Pages: 290
Release: 2002-12-12
Genre: Medical
ISBN: 9780415282079

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The progressive growth of a malignant tumor is accompanied by a decline in the immune response, through mechanisms that have, until recently, been poorly understood. The new era of biological therapies, including cytokines, adoptive transfer of TIL cells, gene therapy and others, brought forth the need to understand the impact of the tumor on the immune system. Moreover, the inability to achieve in humans the unequivocal success of immunotherapy in murine models suggests the possibility that cancer can impair the development of a therapeutic immune response. Scientific and technological advances in cellular and molecular biology during the last two decades have provided new tools with which to explore the dysfunctional immune system of patients with cancer. Novel immunology concepts have provided new insights into changes occurring in tumor cells and the immune system, providing a more cohesive understanding of the process, including: *diminished or absent expression of HLA antigens and co-stimulatory molecules *arrested maturation of dentritic cells *alterations in expression of some signal transduction proteins *increased apoptosis in T and NK cells *presence of suppressor CD+4 and CD25+ T cells Mechanisms of Tumor Escape from the Immune Response provides an introduction to this rapidly developing and, as yet, unsettled area of cancer research, and will be a valuable reference for clinicians and researchers working in the field of cancer immunotherapy.