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Adaptive Immune Resistance in Cancer Therapy by Lin Qi,Zhigang Liu,Ouyang Chen,Hongzhou Cai Pdf
The adaptive immune resistance (AIR) mechanism refers to the various strategies employed by tumours to adapt and ultimately to overcome immune attack. The AIR mechanism was firstly identified in the selective induction of programmed cell death 1 ligand 1 (PDL1) by interferon gamma of tumors. The inhibition of adaptive immune resistance underlies the responses to PD-1 or PD-L1–blocking antibodies, and may have relevance for the development of other cancer immunotherapy strategies. Therefore, identifying specific AIR mechanisms is of great significance to develop novel drugs and enhance the efficacy of cancer treatment. In this research topic, we aim to generate a collection of articles that discuss the AIR mechanisms, the classification of AIRs, and the current and future cancer therapy strategies based on AIR. Of particular, these articles can focus on exploring the AIR mechanisms in different cancer types and further identify the association between AIR and tumour microenvironment (TME).
Once alerted by the innate immune system to the presence of a pathogen or a cellular abnormality, the adaptive immune system responds by activating and expanding antigen-specific B and T lymphocytes. This chapter focuses specifically on the activation and activities of T lymphocytes, which coordinate the adaptive immune response. We open with a description of where and how naïve T cells first encounter antigen. We then examine what factors influence the differentiation of helper CD4+ T lymphocytes into one of several effector subsets, each of which secretes a distinct subset of cytokines. We follow with a discussion of the origin and function of cytotoxic CD8+ T cells, the lymphocyte with the capacity to directly kill tumor cells. We close with a brief summary of the unique challenges that face the adaptive immune system when it tried to mount a response to a tumor.
Immunogenic Cell Death in Cancer: From Benchside Research to Bedside Reality by Abhishek D Garg,Patrizia Agostinis Pdf
Classically, anti-cancer therapies have always been applied with the primary aim of tumor debulking achieved through widespread induction of cancer cell death. While the role of host immune system is frequently considered as host protective in various (antigen-bearing) pathologies or infections yet in case of cancer overtime it was proposed that the host immune system either plays no role in therapeutic efficacy or plays a limited role that is therapeutically unemployable. The concept that the immune system is dispensable for the efficacy of anticancer therapies lingered on for a substantial amount of time; not only because evidence supporting the claim that anti-cancer immunity played a role were mainly contradictory, but also largely because it was considered acceptable (and sometimes still is) to test anticancer therapies in immunodeficient mice (i.e. SCID/athymic mice lacking adaptive immune system). This latter practice played a detrimental role in appreciating the role of anticancer immunity in cancer therapy. This scenario is epitomized by the fact that for a long time the very existence of cancer-associated antigens or cancer-associated ‘danger signaling’ remained controversial. However, over last several years this dogmatic view has been considerably modified. The existence of cancer-associated antigens and ‘danger signaling’ has been proven to be incontrovertible. These developments have together paved way for the establishment of the attractive concept of “immunogenic cell death” (ICD). It has been established that a restricted class of chemotherapeutics/targeted therapeutics, radiotherapy, photodynamic therapy and certain oncolytic viruses can induce a form of cancer cell death called ICD which is accompanied by spatiotemporally defined emission of danger signals. These danger signals along with other factors help cancer cells undergoing ICD to activate host innate immune cells, which in turn activate T cell-based immunity that helps eradicate live (or residual) surviving cancer cells. The emergence of ICD has been marred by some controversy. ICD has been criticized to be either experimental model or setting-specific or mostly a concept based on rodent studies that may have very limited implications for clinical application. However, in recent times it has emerged (through mainly retrospective or prognostic studies) that ICD can work in various human clinical settings hinting towards clinical applicability of ICD. However a widespread consensus on this issue is still transitional. In the current Research Topic we aimed to organize and intensify a discussion that strives to bring together the academic and clinical research community in order to provide a background to the current state-of-the-art in ICD associated bench-side research and to initiate fruitful discussions on present and future prospects of ICD translating towards the clinical, bedside reality.
Author : Stephen Clarke,Bob T. Li Publisher : Karger Medical and Scientific Publishers Page : 90 pages File Size : 48,9 Mb Release : 2017-11-06 Category : Medical ISBN : 9781910797709
Fast Facts: Immuno-Oncology by Stephen Clarke,Bob T. Li Pdf
The treatment of cancer is being revolutionized by drugs that modulate the immune system, offering the prospect of long-term response and extended survival for many patients with advanced incurable cancer. A plethora of new drugs are being incorporated into current standards of care but many questions remain unanswered - and new ones emerge - about how to use these exciting new drugs to best effect. A good understanding of immune-oncology is therefore becoming increasingly important to keep up to date with this rapidly changing field. 'Fast Facts: Immuno-Oncology' takes you from the fundamentals of immunology through to the new concepts of immunoediting and immunotherapy and likely future directions. Whether you are a practicing oncologist, oncology health professional, medical student, cancer researcher or industry professional, this book provides all you need to know about immuno-oncology, concisely summarized. Contents: • Components of the immune system • How cancers evade the immune system • How cancer immunotherapy works • Clinical use of immune checkpoint inhibitors • The future of immuno-oncology • Useful resources
Innate and Adaptive Immunity in the Tumor Microenvironment by Eitan Yefenof Pdf
Traditionally, the interplay between cancer cells and host immunity has been studied systemically. Recent studies, however, indicate that the tumor microenvironment is unique in providing both supportive and inhibitory factors that determine the fate of the tumor and its host. This volume compiles reviews on innate and adaptive immune responses at the tumor microenvironment with emphasis on positive and negative outcomes that affect the progression of the disease.
Cancer Immunotherapy by Lauren M.F. Merlo,Laura Mandik-Nayak Pdf
B cells provide a variety of important functions to the adaptive immune system including antibody production, antigen presentation, and cytokine secretion, as well as being required for the development of proper lymphoid architecture. B cells originate in the bone marrow, where they mature and produce an initial diverse repertoire of non-self reactive B-cell receptors. After moving to the periphery, naïve B cells are presented with antigen by dendritic and other antigen-presenting cells. B cells that come in contact with and can recognize antigen become activated, expand, and further alter the B-cell receptor to improve antigen specificity through somatic hypermutation and affinity maturation. This B-cell receptor is subsequently secreted as active, mature antibody. Antibodies are able to recognize and bind to bacteria, viruses, and other antigens, initiating a cascade of processes that rid the body of pathogens.
Author : George C. Prendergast,Elizabeth M. Jaffee Publisher : Elsevier Inc. Chapters Page : 684 pages File Size : 46,6 Mb Release : 2013-06-04 Category : Medical ISBN : 9780128058978
Cancer Immunotherapy by George C. Prendergast,Elizabeth M. Jaffee Pdf
Immunological thought is exerting a growing effect in cancer research, correcting a divorce that occurred in the mainstream of the field decades ago as cancer genetics began to emerge as a dominant movement. During the past decade, a new general consensus has emerged among all cancer researchers that inflammation and immune escape play crucial causal roles in the development and progression of malignancy. This consensus is now driving a new synthesis of thought with great implications for cancer treatments of the future. This book introduces new concepts and practices that will dramatically affect oncology by adding new immune modalities to present standards of care in surgery, radiotherapy and chemotherapy. Its aim is to cross-fertilize ideas in the new area of immunochemotherapy, which strives to develop new combinations of immunological and pharmacological agents as cancer therapeutics. Specifically, our goals are to (1) highlight novel principles of immune suppression in cancer, which represent the major salient breakthroughs in the field of cancer immunology the last decade, and to (2) discuss the latest thinking in how immunotherapeutic and chemotherapeutic agents might be combined, not only to defeat mechanisms of tumoral immune suppression but also to reprogram the inflammatory microenvironment of tumor cells to enhance the long-term outcomes of clinical intervention. Many immune-based therapies have focused on activating the immune system. However, it is now clear that these therapies are often thwarted by the ability of cancers to erect barricades that evade or suppress the immune system. Mechanistic insights into these barricades have enormous medical implications, not only to treat cancer but also many chronic infectious and age-associated diseases where relieving pathogenic immune tolerance is a key challenge. In this book, contributors with a wide diversity of perspectives and experience provide an introductory overview to the immune system; how tumors evolve to evade the immune system; the nature of various approaches used presently to treat cancer in the oncology clinic; and how these approaches might be enhanced by inhibiting important mechanisms of tumoral immune tolerance and suppression. The overarching aim of this treatise is to provide a conceptual foundation to create a more effective all-out attack on cancer. This chapter offers a historical perspective on the development of immunological thought in cancer, a discussion of some of the fundamental challenges to be faced, and an overview of the chapters which frame and address these challenges.
Systems Biology in Cancer Immunotherapy by Mahbuba Rahman Pdf
Over the past decades, systems biology approaches have been applied in different areas of life science research including oncology. Researchers now understand the hallmarks of cancer cells such as abnormal cell growth, inflammation, dysregulated metabolic pathways and drug resistance properties at a molecular level. Systems biology approaches have enabled researchers to investigate cancer immunology by identifying cancer related biomarkers on immune cells, and to study the effect of different therapies in tissue cultures and mouse models. Systems Biology in Cancer Immunotherapy explains the scope of systems biology in understanding the immune response to neoplasms. The book introduces readers to the concepts crucial to cancer immunology before delving into the applied systems biology topics such as the metabolic pathways in cancer cells, the biomolecular roles of signal transduction molecules and their respective biochemical pathways ad cancer immunotherapy. A brief conclusion at the end also provides some information from a clinical and commercial perspective on cancer immunotherapy. This volume is intended as an introductory reference for life science and medical students, researchers and academics interested in the application of systems biology to the immune system in oncology research and chemotherapy practice.
Understanding convergent evasion mechanisms in cancer and chronic infection: Implications for immunotherapy by Matthias Theobald,Hansjörg Schild Pdf
The complex interactions between the innate and adaptive immune systems function to recognize and clear pathogens or transformed cells, but inefficient interactions between these two systems can result in harmful immunologic responses including chronic infections and the development of cancer. Several hallmarks of dysfunctional adaptive immune responses often detected in tumors share specific features with ineffective immunity in chronic infections. The members of the micromilieu actively participate in the process of tumorigenesis or chronification of infection by modulating innate and adaptive immune system interactions leading e.g. to insufficient T cell responses. The best example is given by the acquisition of an “exhausted” state of cytotoxic CD8+ T cells (CTLs) responding to chronic infections or tumors that are associated with elevated expression of inhibitory receptors and impaired cytokine response. Targeting these major inhibitory pathways by immune checkpoint blockers represents a prime example of successful clinical translation of tumor-specific immunotherapies. Understanding the mechanisms behind (mal)adaptations of the immune system is crucial for achieving therapeutic benefits. The establishment and co-evolution of a dynamic microenvironment niche constituted by the recruitment of numerous cell types dampen immune responses and thus contribute to the development of neoplastic transformation as well as infection. Although there are examples of successful immunotherapeutic approaches (CAR-T cells, immune checkpoint inhibitors, or mRNA vaccination), a large percentage of patients with cancer or chronic infections still do not benefit from these therapies or develop severe immune-related adverse events. The reasons for these failures are not well understood. A possible explanation might be that current immunotherapies target predominantly the effector arm of the immune system by trying to reactivate dysfunctional T cells, but do not sufficiently address the influence of the innate immune system and the contributions of the tumor microenvironment (TME) niche. The main problem we would like to address in this special issue is how inappropriate function of the innate immune system affects adaptive immunity and contributes to inefficient anti-cancer immunity and chronification of infections. The central goal is to provide a more precise understanding of the various (common and novel) immune evasion mechanisms in cancers and in chronic infections to obtain a detailed map of common and disease-specific immune escape checkpoints. To that aim, we want to compile a wide array of interdisciplinary studies exploring a comparative and multi-layered analysis of mechanisms responsible for inefficient immune responses, including novel approaches i.e. multi-omics or epigenetic signaling. We would also like to combine studies from different fields, including basic and clinical immunology, oncology, and virology/microbiology. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case report, and Perspective articles that cover, but are not limited to the following topics: • Convergent mechanisms supporting immune escape in preclinical models (tumors and chronic infections) • Convergent evasion mechanisms mediated by tumor-infiltrating suppressive cells (Treg, MDSC, macro-phages, soluble mediators, signaling, metabolism, ...) • Convergent immune evasion mechanisms mediated by chronic infection (viral or parasite) • Novel strategies to modulate the TME by direct or indirect targeting of immune suppressor cells. • Approaches to enhance persistence and resilience of anticancer T cells • Combinatorial therapeutic strategies (mRNA, antibodies, immune checkpoint blockers …) that target convergent immune evasion mechanisms Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Interaction of Immune and Cancer Cells by Magdalena Klink,Izabela Szulc-Kielbik Pdf
Now, it its second edition, this book summarizes the role of immune cells in tumor suppression and progression. It describes in detail why tumor cells can survive and spread in spite of the antitumor response of immune cells. Since immunotherapy is an attractive approach to cancer therapy, this book also provides information on the two main strategies: monoclonal antibodies and adaptive T cell immunotherapy, with a focus on recent human clinical trials. A newly added chapter also focuses on the role of Natural Killer cells in tumor progression. The book provides a state-of-the-art, comprehensive overview of immune cells in cancer and is an indispensable resource for researchers and practitioners working or lecturing in the field of cancer research and immunology.
Author : Mary L. Disis Publisher : Springer Science & Business Media Page : 516 pages File Size : 44,8 Mb Release : 2007-10-28 Category : Medical ISBN : 9781597450119
Expert bench and clinical scientists join forces to concurrently review both the state-of-the-art in tumor immunology and its clinical translation into promising practical treatments. The authors explain in each chapter the scientific basis behind such therapeutic agents as monoclonal antibodies, cytokines, vaccines, and T-cells, and illustrate their clinical manipulation to combat cancer. Additional chapters address statistical analysis-both of clinical trials and assay evaluations-methods for the discovery of antigens, adoptive T cell therapy, and adaptive and innate immunity. The challenges in clinical trial design, the need for biomarkers of response-such as novel imaging techniques and immunologic monitoring-and the new advances and directions in cancer immunotherapy are also fully examined.
Tumor Immunology and Immunotherapy by Robert C. Rees Pdf
Patients are beginning to benefit from antibody based, cellular and vaccine approaches that are effective against genetically diverse and therapy-resistance cancers. BCG immunotherapy is now being used as a first line treatment for human bladder cancer and the introduction of prophylactic vaccination against Hepatitis B and HPV cancers is starting to show positive results. Following recent FDA approval for a vaccination against prostate cancer, and optimistic results in clinical trials for a vaccine targeting cancer antigens in lung cancer, cancer immunotherapy is now significantly impacting patient clinical management. Tumor Immunology and Immunotherapy provides an up-to-date and comprehensive account of cancer immunity and immunotherapy. It discusses our adaptive and innate immunity to cancer, the mechanisms underpinning our immune response, current approaches to cancer immunotherapy, and how tumour and host responses can circumvent effective anti-cancer immunity. The book examines recent results, publications and current areas of interest including 'immune editing' and the specific issues that are affecting the research and development of vaccines, providing insight into how these problems may be overcome, as viewed by world leaders in the field. Tumor Immunology and Immunotherapy will appeal to clinicians working in oncology and cancer immunotherapy, and research scientists including PhD and masters students, post-doctoral researchers and senior investigators.
The human immune system is arguably the most complex system in the human body. It is comprised of dozens of completely distinct cell types, each with its own set of signaling molecules, antigen-recognition mechanisms and effector functions. This complexity allows the immune system to respond to the potentially millions of distinct foreign antigens that it might encounter, from bacteria, viruses and other microscopic pathogens, to the body’s own cells when they go awry in diseases such as cancer. This chapter provides an overview of the central cellular architecture of the immune system and describes the ways in which its cells are regulated during the immune response. We are now entering an era in which we have a sufficiently deep understanding of these fundamental regulatory mechanisms that they can be harnessed to provide a highly selective therapeutic strategy for targeting cancer cells.
Author : Howard L. Kaufman,Jedd D. Wolchok Publisher : Springer Science & Business Media Page : 502 pages File Size : 47,5 Mb Release : 2007-10-12 Category : Medical ISBN : 9781402060878
General Principles of Tumor Immunotherapy by Howard L. Kaufman,Jedd D. Wolchok Pdf
This book brings together the world’s leading authorities on tumor immunology. This book describes the basic immunology principles that form the foundation of understanding how the immune system recognizes and rejects tumor cells. The role of the innate and adaptive immune responses is discussed and the implications of these responses for the design of clinical strategies to combat cancer are illustrated.
Cancer Immunotherapy by George C. Prendergast,Elizabeth M. Jaffee Pdf
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
