Enhancing Immune Therapy For Cancer By Targeting Myeloid Derived Suppressor Cells
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Author | : Andrew Robert Stiff |
Publisher | : |
Total Pages | : |
Release | : 2017 |
Genre | : Immune system |
ISBN | : |
While some of the mechanisms that cause impaired NK cell and T cell function are linked to processes inherent to tumor cells such as cytokine production and metabolic alterations it is also clear that cancer is linked to the expansion of multiple immune suppressive cell populations such as regulatory T cells (Treg), tumor associated macrophages (TAMs), and myeloid derived suppressor cells (MDSC).
Author | : David Escors |
Publisher | : Springer |
Total Pages | : 109 |
Release | : 2016-03-15 |
Genre | : Medical |
ISBN | : 331926821X |
The book starts with an introduction to and history of myeloid-derived suppressor cells (MDSCs), followed by a description of their differentiation, their role in the tumour microenvironment and their therapeutic targeting. It closes with an outlook on future developments. In cancer patients, myelopoiesis is perturbed and instead of generating immunogenic myeloid cells (such as dendritic cells, inflammatory macrophages and granulocytes), there is an increase in highly immature MDSCs. These cells are distributed systemically, resulting in general immunosuppression. They also infiltrate tumours, promoting their progression and metastasis by inhibiting the natural anti-tumour immune response. As these cells also interact with classical anti-neoplastic treatments, they have become major therapeutic targets in the pharmaceutical industry and in oncology research.
Author | : George C. Prendergast |
Publisher | : Academic Press |
Total Pages | : 679 |
Release | : 2013-06-04 |
Genre | : Medical |
ISBN | : 0123946336 |
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
Author | : Saul J. Priceman |
Publisher | : Elsevier Inc. Chapters |
Total Pages | : 33 |
Release | : 2013-06-04 |
Genre | : Medical |
ISBN | : 0128059222 |
Tumor-associated immune cells, in particular myeloid cells, have opposing roles during cancer development by facilitating antitumor immune responses and driving cancer-promoting inflammation. Defective antitumor immunity is prevalent in cancers, and it is now clear that overcoming the myeloid cell-mediated immunosuppressive microenvironment poses tremendous interest for future cancer therapies. JAK/STAT signaling has come to the forefront as a crucial pathway to induce immunosuppression and procancer inflammation. Specifically, STAT3 activation is critical for the phenotype of myeloid cells by regulating immunosuppressive and prometastatic factors, thereby providing myeloid cells with a multitude of tumor-promoting functions. Genetic ablation of STAT3 in the myeloid compartment induces potent innate and adaptive antitumor immunity along with an inhibition of tumor growth and metastasis. Recently, therapeutic targeting of JAK/STAT3 has shown great promise in blocking immunosuppression in preclinical models. One such example is the use of novel siRNA to selectively target STAT3 in myeloid cells, through conjugation to CpG oligonucleotides that agonize Toll receptor TLR9 on myeloid cells. Along with other novel therapeutic strategies to inhibit JAK/STAT signaling, it seems likely that future efforts to target this pathway will be made in single and combination approaches for effective anticancer immunotherapy.
Author | : Salem Chouaib |
Publisher | : Frontiers Media SA |
Total Pages | : 196 |
Release | : 2020-07-02 |
Genre | : |
ISBN | : 2889638170 |
Author | : Suzanne Ostrand-Rosenberg |
Publisher | : Elsevier Inc. Chapters |
Total Pages | : 50 |
Release | : 2013-06-04 |
Genre | : Medical |
ISBN | : 0128059249 |
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.
Author | : Maija Hollmén |
Publisher | : Frontiers Media SA |
Total Pages | : 150 |
Release | : 2020-01-24 |
Genre | : |
ISBN | : 2889633934 |
Author | : Olivera J. Finn |
Publisher | : Frontiers Media SA |
Total Pages | : 162 |
Release | : 2020-05-06 |
Genre | : |
ISBN | : 2889636771 |
Myeloid Derived Suppressor Cells (MDSCs) are a heterogeneous population of immature myeloid cells that can suppress the function of multiple immune cells and in particular, T cells, through various mechanisms. MDSCs can be divided into two major subtypes based on their cell surface phenotype and morphology: polymorphonuclear MDSC (PMN-MDSC or G-MDSC) and monocytic MDSC (M-MDSC). Additional subtypes have been proposed, such as the early MDSC (e-MDSC) that lack both macrophage and granulocyte markers. There is still considerable ambiguity about the phenotype of these cells that corresponds to their immunosuppressive function and there are on-going challenges on how to identify, purify and/or potentially generate and expand these cells in vitro. MDSCs were first discovered in cancer patients where they have been most extensively studied as components of the immunosuppressive tumor microenvironment. In the last several years, however, the importance of their immunomodulatory role in many other disease and clinical settings has emerged. Acknowledgments We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.
Author | : Dmitry I. Gabrilovich |
Publisher | : Springer Science & Business Media |
Total Pages | : 471 |
Release | : 2014-02-10 |
Genre | : Medical |
ISBN | : 1489980563 |
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 | : Dmitry I. Gabrilovich |
Publisher | : Springer Science & Business Media |
Total Pages | : 304 |
Release | : 2008-01-01 |
Genre | : Medical |
ISBN | : 0387691189 |
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.