More than 200,000 American women are diagnosed with breast cancer each year. Although therapies effective in treating metastatic breast cancer currently exist, each year approximately 40,000 women die from this disease. Current evidence indicates that anti-cancer immune responses can be induced by vaccination in situ to the growth of metastasis and protect patients from the tumor recurrence. However, induction of anticancer immune responses may be limited in their efficacy due to immune suppression mechanisms induced by the developing cancer. Myeloid-derived suppressor cells are one population of immune regulators comprised of immature cells of myeloid origin with important roles in blocking immune activation and promoting tumor progression. Elimination or maturation of these cells has been found to promote enhanced anti-tumor effects and improve overall survival. This thesis identifies a new role for interleukin-12 as a modulator of myeloid-derived suppressor cell activity. Interleukin-12 was found to promote up-regulation of cell maturation markers on the surface of myeloid-derived suppressor cells with an accompanying decrease in factors responsible for conferring suppressive activity such as nitric oxide synthase 2 and arginase I. The alterations in myeloid-derived suppressor cells were observed following both in vitro and in vivo treatment with interleukin-12. Further analysis of the anti-tumor efficacy of interleukin-12 revealed that at least part of its suppression of tumor growth can be linked to reductions in myeloid-derived suppressor cell populations in the tumor microenvironment and an influx of active CD8+ T cells into the tumor microenvironment. The findings outlined in this thesis show that interleukin-12 alters the suppressive function of myeloid-derived suppressor cells leading to significant immune infiltration and activation resulting in increased overall survival and a reduction in metastasis.

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.

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.

Translational Immunotherapy of Brain Tumors gives researchers and practitioners an up-to-date and comprehensive overview of the field. Chapters include adoptive immunotherapy, immunosuppression, CAR therapy of brain tumors, and dendritic cell therapy for brain tumors. Very few agents have been shown to be efficacious in the treatment of malignant gliomas. Recently, there have been a number of studies demonstrating the potential success of immunotherapy for brain tumors. Immunotherapeutics are becoming the most frequent drugs to be used in cancer therapy. These new breakthroughs, now approved by the FDA, are a part of multiple phase III international trials and ongoing research in malignant glioma, meaning that the information in this cutting-edge book will be of great importance to practitioners and researchers alike. Comprehensive overview, providing an update on immunology, translational immunotherapy, and clinical trials relating to malignant gliomas Edited by a prominent neurosurgeon with contributions by leading researchers in the field Ideal resource for researchers and practitioners interested in learning about mechanisms that use the immune system to treat brain tumors

Analysis of multidirectional immunological responses at the tumor site allows forming a new concept of The Tumor Immunoenvironment, which is introduced and discussed in the present book with a particular focus on the role of immune cells in controlling the tumor microenvironment at different stages of cancer development. The main goal of this publication is to provide an overview of the current knowledge on the complex and unique role of the immune system, tumor-associated inflammation and tumor-mediated immunomodulation in cancer progression in a way that allows understanding the logistics of cellular and molecular interactions in the tumor lesions.

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.

This book summarizes the progress in studies of tuberculosis host-pathogen interactions from several perspectives: molecular microbiology, immunology, animal models, clinical studies, epidemiology, and drug discovery. Tuberculosis (TB) remains a severe global public health problem. Complex interactions between environmental, microbial and host factors lead to clinically relevant infections. Studies on bacterial virulence, host-genetic, and immunological factors contributing to the susceptibility to TB provide an ever-growing foundation of knowledge that is critical to finding new interventions. Studies of immune mechanisms against M. tuberculosis infection have identified immunological markers associated with specific phenotypes in the host, providing insight into how they may be used to augment current treatment strategies. Recent advances in diagnosis, therapeutics and vaccines, as well as basic-research oriented studies have shed light on the development of new directions for prevention, treatment and control of TB. Improved understanding of the interplay between the bacterium and host is a key component of reducing incidence worldwide.

Of the two disciplines in parallel development for two decades, tumor immunology and transplantation immunology, the latter has thrived and has led to some of the most critical discoveries in immunobiology. The former continues to thwart both scientists and clinicians alike.The goal of immunologists in modern day research is to develop a simple and effective means to manipulate cancer in vivo, possibly encompassing several venues: identifying a phenotypic marker and the use of either active or passive immunization; include the use of passive reagents carrying "warheads" to selectively destroy cancer cells; or altering the basic process of cell survival.This excellent multidiscipline-authored volume presents a theme which has not been well described before. The papers include both basic and clinical science and range from sophisticated molecular biology to little more than phenomenology (e.g. the increased association of cancer in some autoimmune diseases and increased presentation of autoimmune phenomena in malignant condition). This, however, is state-of-the-art.This collection of themes will be of use not only to bench scientists, but also to clinicians who treat patients. The book represents progress at the cutting edge of this discipline, and points the way to further developments in the "black box" of immunology.

A link between inflammation and cancer has been established many years ago, yet it is only recently that the potential significance of this connection has become apparent. Although several examples of chronic inflammatory conditions, often induced by persistent irritation and/or infection, developing into cancer have been known for some time, there has been a notable resistance to contemplate the possibility that this association may apply in a causative way to other cancers. Examples for such progression from chronic inflammation to cancer are colon carcinoma developing with increased frequency in patients with ulcerative colitis, and the increased incidence of bladder cancer in patients suffering from chronic Schistosoma infection. Inflammation and cancer have been recognized to be linked in another context for many years, i.e., with regards to pathologies resembling chronic lacerations or 'wounds that do not heal.' More recently, the immunology of wound healing has given us clues as to the mechanistic link between inflammation and cancer, in as much as wounds and chronic inflammation turn off local cell-mediated immune responses and switch on growth factor release as well the growth of new blood vessels - angiogenesis. Both of these are features of most types of tumours, which suggest that tumours may require an immunologically shielded milieu and a growth factor-rich environment.

For the first time, each volume stands alone as an example of the best writing in the fields of bacteriology, immunology, mycology, parasitology and virology. Together they work as a set - answering every conceivable query in this vast and growing field