Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino acid tryptophan independent of the process that maintains normal tryptophan homeostasis. In recent years, interest in IDO and the tryptophan catabolic pathway it feeds into has grown rapidly with the discovery that IDO activity is critical for generating tolerance to foreign antigens in a variety of tissue microenvironments. In cancer, IDO is overexpressed in both tumor cells and stromal cells where it promotes the establishment of peripheral tolerance to tumor antigens. By helping tumor cells escape T-cell-dependent immune attack, IDO contributes to pathogenic inflammatory states which permit tumor survival and outgrowth. In preclinical studies, small molecule inhibitors of IDO can reverse this mechanism of immune escape. Notably, in combinatorial treatment regimens, IDO inhibition strongly leverages the efficacy of classical cancer chemotherapeutic agents, causing the regression of tumors that are otherwise largely resistant to treatment. Based on these findings, clinical evaluation of IDO inhibitors for cancer treatment is currently ongoing. After presenting a historical background on the discovery and early studies of this enzyme, this chapter focuses on work that defines IDO as an important mediator of pathogenic inflammation and cancer, and summarizes the development of IDO inhibitors as potential anticancer modalities.
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.
Since the Kierkegaard Studies Monograph Series (KSMS) was first published in 1997, it has served as the authoritative book series in the field. Starting from 2011 the Kierkegaard Studies Monograph Series will intensify the peer-review process with a new editorial and advisory board. KSMS is published on behalf of the Søren Kierkegaard Research Centre at the University of Copenhagen. KSMS publishes outstanding monographs in all fields of Kierkegaard research. This includes Ph.D. dissertations, Habilitation theses, conference proceedings and single author works by senior scholars. The goal of KSMS is to advance Kierkegaard studies by encouraging top-level scholarship in the field. The editorial and advisory boards are deeply committed to creating a genuinely international forum for publication which integrates the many different traditions of Kierkegaard studies and brings them into a constructive and fruitful dialogue. To this end the series publishes monographs in English and German. Potential authors should consult the Submission guidelines. All submissions will be blindly refereed by established scholars in the field. Only high-quality manuscripts will be accepted for publication. Potential authors should be prepared to make changes to their texts based on the comments received by the referees.
Technology shapes every aspect of contemporary life, but George Pattison argues that thinking about God offers a creative counter-movement to the dominant technological culture. His argument is applied to questions of ethics, university study, the arts, and urban living.
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