Autoimmuno Anti Tumour Immunity Aati Understanding The Immune Responses Against Self Altered Self

The brief description of tumours being “wounds that do not heal” by Dr Harold F. Dworak nearly three decades ago (N Engl J Med 1986) has provided not only a vivid illustration of neoplastic diseases in general but also, in retrospect conceptually, a plausible immunological definition of cancers. Based on our current understanding in the field, it could have even a multi-dimensional meaning attached with. This relates to several important issues which need to be addressed further, i.e. in terms of a close link between chronic inflammation and tumourigenesis widely observed; clinical and experimental evidence of immunity against tumours versus the highly immunosuppressive tumour microenvironment being associated; and their underlying immunological mechanisms, oncogenic basis, as well as the true causal relationship in question. Recent findings from studies into the pathogenesis of autoimmunity and, more importantly, the mechanisms which protect against it, have offered some new insights for our understanding in this direction. Chronic or persistent autoimmune-like inflammatory conditions are evidently associated with tumor development. The important question is about their true causal relationship. Chronic or persistent inflammation has been shown to contribute directly to tumour development by triggering neoplastic transformation and production of inflammatory mediators which could promote cancer cell survival, proliferation and invasion. On the other hand, tumours are mutated self-tissue cells to which the host immune system is largely tolerized otherwise. Although the mutations may give rise to the expression of tumour-specific antigens (TSA) or tumour-associated antigens (TAA), most of these TSAs/TAAs are found to be poor immunogens. The ongoing inflammatory conditions may therefore reflect a desperate attempt of the host immune system to mount anti-tumour responses, though ineffectively, being a consequence of the continuous yet largely futile triggering by those poorly immunogenic TSAs/TAAs. Furthermore, during autoimmune or overtly persistent immunological responses, many regulatory mechanisms are triggered in the host in attempts to limit the ongoing harmful inflammatory reactions. Such a negative feedback regulation is known to be crucial in preventing normal individuals from immune-mediated diseases. As a result of the negative feedback loop, however, an excessive production of anti-inflammatory or immunosuppressive molecules followed by the exhaustion of the immune effector cells may instead lower the ability of the host immune system to mount specific anti-tumor responses, allowing the escape of tumour or mutated cells from immunosurveillance. This may also help to explain why the most effective way to enhance host immunity against cancer is by targeting the negative arm of immune regulation. In this Frontiers Research Topic, we aim to gather current views from experts in these inherent overlapping fields of oncology, autoimmunity and tumour immunology, and to make them available to our potential readership who may be particularly interested in this cutting-edge area. By understanding how the immune system is normally regulated, why dysregulation of which may cause the immunological-oncological related diseases, we also encourage further discussions as to how the so-called "self-reactivity" (autoimmune responses) can be alternatively switched on and redirected, immunologically or molecularly, for effective cancer treatment.

The brief description of tumours being "wounds that do not heal" by Dr Harold F. Dworak nearly three decades ago (N Engl J Med 1986) has provided not only a vivid illustration of neoplastic diseases in general but also, in retrospect conceptually, a plausible immunological definition of cancers. Based on our current understanding in the field, it could have even a multi-dimensional meaning attached with. This relates to several important issues which need to be addressed further, i.e. in terms of a close link between chronic inflammation and tumourigenesis widely observed; clinical and experimental evidence of immunity against tumours versus the highly immunosuppressive tumour microenvironment being associated; and their underlying immunological mechanisms, oncogenic basis, as well as the true causal relationship in question. Recent findings from studies into the pathogenesis of autoimmunity and, more importantly, the mechanisms which protect against it, have offered some new insights for our understanding in this direction. Chronic or persistent autoimmune-like inflammatory conditions are evidently associated with tumor development. The important question is about their true causal relationship. Chronic or persistent inflammation has been shown to contribute directly to tumour development by triggering neoplastic transformation and production of inflammatory mediators which could promote cancer cell survival, proliferation and invasion. On the other hand, tumours are mutated self-tissue cells to which the host immune system is largely tolerized otherwise. Although the mutations may give rise to the expression of tumour-specific antigens (TSA) or tumour-associated antigens (TAA), most of these TSAs/TAAs are found to be poor immunogens. The ongoing inflammatory conditions may therefore reflect a desperate attempt of the host immune system to mount anti-tumour responses, though ineffectively, being a consequence of the continuous yet largely futile triggering by those poorly immunogenic TSAs/TAAs. Furthermore, during autoimmune or overtly persistent immunological responses, many regulatory mechanisms are triggered in the host in attempts to limit the ongoing harmful inflammatory reactions. Such a negative feedback regulation is known to be crucial in preventing normal individuals from immune-mediated diseases. As a result of the negative feedback loop, however, an excessive production of anti-inflammatory or immunosuppressive molecules followed by the exhaustion of the immune effector cells may instead lower the ability of the host immune system to mount specific anti-tumor responses, allowing the escape of tumour or mutated cells from immunosurveillance. This may also help to explain why the most effective way to enhance host immunity against cancer is by targeting the negative arm of immune regulation. In this Frontiers Research Topic, we aim to gather current views from experts in these inherent overlapping fields of oncology, autoimmunity and tumour immunology, and to make them available to our potential readership who may be particularly interested in this cutting-edge area. By understanding how the immune system is normally regulated, why dysregulation of which may cause the immunological-oncological related diseases, we also encourage further discussions as to how the so-called "self-reactivity" (autoimmune responses) can be alternatively switched on and redirected, immunologically or molecularly, for effective cancer treatment.

In 1956, three groups independently reported evidence that some thyroid disease appearing spontaneously in humans or experimentally induced in animals are related to autoimmune processes. The interval between these landmark discoveries and the present has witnessed a remarkable and continuing growth of both knowledge and concepts concerning the mechanisms of immune regulation, the pathogenesis of autoimmune thyroid diseases, and their clinical and laboratory manifestations. More importantly knowledge of thyroid autoimmunity has, in many respects, comprised the vanguard of an ever increasing appreciation and understanding of autoimmune diseases in general. On November 24-26 1986, an International Symposium on Thyroid Autoimmunity was held in Pisa. Its purpose was to commemorate the birth of thyroid autoimmunity as a scientific discipline, to summarize current knowledge and concepts in this area, and where possible, to anticipate areas of opportunity for the future - hence the theme of the Symposium, Memories and Perspectives. To open the meeting, the Magnifico Rettore (Chancellor) of the University of Pisa granted special Awards to Dr. Deborah Doniach, Dr. Ivan Roitt, and Dr. Noel R. Rose, who published the first fundamental studies in the field of thyroid autoimmunity, and to Dr. Duncan G. Adams, whose discovery of the long-acting thyroid stimulator (LATS) opened the door to our current understanding of the pathogenesis of Graves' disease. During the meeting thirty plenary lectures were presented.

In order to understand common conditions such as coeliac disease and Crohn’s disease, one must view the gut in its evolutionary context. This is the novel approach to the gut and its diseases that is adopted in this book. The first part tells the story of the evolution of the gut itself – why it came about and how it has influenced the evolution of animals ever since. The second part focuses on the evolution of immunity and how the layers of immune mechanisms are retained in the gut, resembling the strata revealed in an archeological dig. The final part, ‘The Gastro-Archeologist’, ties the first two together and highlights how understanding the gut and immune system in their evolutionary context can help us understand diseases affecting them. Ambitious in its scope but telling a unique story from a refreshingly novel perspective, the book offers an informative and enjoyable read. As the story of the gut, immunity and disease unfolds, the author aims to endow readers with the same sense of awe and excitement that the subject evokes in him. Difficult concepts are illustrated using simple and colourful analogies, and the main content is supplemented with anecdotes and unusual and amusing facts throughout the book. The book is intended for anyone with an interest in the gut, its immunity and diseases, ranging from school and college biology and biomedical students, to professionals working in the field, and to patients suffering from intestinal diseases who want to understand more about their conditions.

Follow along as this New York Times bestselling author details the astonishing scientific discovery of the code to unleashing the human immune system to fight in this "captivating and heartbreaking" book (The Wall Street Journal). For decades, scientists have puzzled over one of medicine's most confounding mysteries: Why doesn't our immune system recognize and fight cancer the way it does other diseases, like the common cold? As it turns out, the answer to that question can be traced to a series of tricks that cancer has developed to turn off normal immune responses -- tricks that scientists have only recently discovered and learned to defeat. The result is what many are calling cancer's "penicillin moment," a revolutionary discovery in our understanding of cancer and how to beat it. In The Breakthrough, New York Times bestselling author of The Good Nurse Charles Graeber guides readers through the revolutionary scientific research bringing immunotherapy out of the realm of the miraculous and into the forefront of twenty-first-century medical science. As advances in the fields of cancer research and the human immune system continue to fuel a therapeutic arms race among biotech and pharmaceutical research centers around the world, the next step -- harnessing the wealth of new information to create modern and more effective patient therapies -- is unfolding at an unprecedented pace, rapidly redefining our relationship with this all-too-human disease. Groundbreaking, riveting, and expertly told, The Breakthrough is the story of the game-changing scientific discoveries that unleash our natural ability to recognize and defeat cancer, as told through the experiences of the patients, physicians, and cancer immunotherapy researchers who are on the front lines. This is the incredible true story of the race to find a cure, a dispatch from the life-changing world of modern oncological science, and a brave new chapter in medical history.

This book is about three inflammatory conditions that underlie wheat sensitivities caused by the consumption of wheat and related cereals. The book describes, discusses and differentiates celiac disease, amylase trypsin inhibitor (ATI) sensitivity, and the wide spectrum of wheat allergies, especially a novel, but highly common atypical wheat allergy. The mechanisms of the three wheat sensitivities along with their clinical characteristics, and their their state-of-the art diagnosis and therapy are thoroughly described. This is accompanied by commented case reports. The book is well structured and illustrated with numerous easy-to-grasp yet scientifically updated sketches. The novelty, immunological insight and praxis relevance for specialists as well as patients and interested laypeople makes this book appealing to a broad readership. Written by an internationally distinguished scientist and clinician in food and wheat related diseases, this book is intended for GPs, internists, gastroenterologists, rheumatologists and immunologists, as well as dieticians, researchers and especially patients who might be affected by these sensitivities.