This volume illustrates the salient aspects of cancer biology relevant to the successful implementation of immunotherapy. Topics include enhancement of antigen-specific immune responses by anti-cancer vaccines, modulation of the function of T cells within the tumor microenvironment, and the effects of genetic, epigenetic, developmental, and environmental determinants on T cell function. Other topics covered include the ex vivo expansion of T or other immune cells and their genetic modification or reprogramming to increase their ability to survive and expand when adoptively transferred back to the patients. Specific attention is devoted to the genetic manipulation of T cells through the introduction of re-directed T cell receptors, chimeric antibody receptors, and other genetic manipulation aimed at improving their effectiveness as anti-cancer agents. Furthermore, the revolutionary role of checkpoint inhibitors and their potential in combination with other immunotherapeutic approaches or with standard chemo and radiation therapy are extensively discussed.

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.

Tumors that become clinically apparent have invariably developed ways to escape immune control. The mechanisms of escape are multiple and diverse and do not necessarily require the loss by tumor cells of expression of antigens recognized by the immune system. More commonly, tumor-specific T cells are rendered dysfunctional by a number of soluble and cell surface-bound molecules that are produced or modified by the action of cancer cells or suppressive and regulatory immune cells recruited to the tumor. Overall, the obstacles that prevent tumor rejection are active at several levels, affecting T-cell priming, functional differentiation, recruitment to the tumor, survival and effectors’ function inside the tumor. The multifaceted nature of these immunosuppressive networks represents a formidable obstacle to the success of immunotherapy. Nevertheless, the recent achievements of therapeutics targeting key checkpoint receptors highlight the great potential of strategies that are based on selective disruption of immunosuppressive networks.

Revealing essential roles of the tumor microenvironment in cancer progression, this book focuses on the role of hematopoietic components of the tumor microenvironment. Further, it teaches readers about the roles of distinct constituents of the tumor microenvironment and how they affect cancer development. Topics include neutrophils, basophils, T helper cells, cytotoxic lymphocytes, fibrocytes, and myeloid-derived suppressor cells, and more. Taken alongside its companion volumes, these books update us on what we know about various aspects of the tumor microenvironment as well as future directions. Tumor Microenvironment: Hematopoietic Cells – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

This volume discusses novel concepts in cancer biology, focusing on different factors that affect the tumor microenvironment. Topics covered include sex-based differences in the tumor microenironment, dormancy in the tumor microenvironment, the influence of obesity on the tumor microenvironment, and much more. Taken alongside its companion volumes, Tumor Microenvironment: Novel Concepts covers the latest research on various aspects of the tumor microenvironment, as well as future directions. Useful for introducing the newer generation of researchers to the history of how scientists studied the tumor microenvironment as well as how this knowledge is currently applied for cancer treatments, it will be essential reading for advanced cell biology and cancer biology students, as well as researchers seeking an update on research on the tumor microenvironment.

Over the past century, the identification of molecules that tumor cells utilize to manipulate the activation or survival of immune cells has proven difficult. Expression analyses have helped to discover the downregulation of PD-L1, TGF-[beta] , and FasL in the tumor microenvironment. Mutation analyses have helped identify novel tumor-specific or -associated antigens presented to the cell surface through major histocompatibility (MHC) complexes. Unfortunately, these techniques often fail to recognize the complex cross-talk occurring between cells in the tumor microenvironment to influence the anti-cancer immune response. By employing an RNAi screen in vivo, we have parsed how gene knockdown in tumor cells affects the ability of the immune system to identify and eliminate malignant cells. To identify tumor cell derived immune modulators, the EO771 breast adenocarcinoma cell line derived from a C57Bl/6 mice was transduced via lentiviral vectors with a barcoded genome-wide murine shRNA library and engrafted in immune-competent and immune-deficient mice. By analyzing the relative shRNA representation in tumors grown in the presence of a functional adaptive immune system compared to those grown in immune-deficient mice, we discovered a subset of tumor-based genes whose knock-down affects immune recognition. Pathway analysis identified enrichment of shRNAs targeting previously identified immune regulators, including the TGF-[beta]R pathway and MHC class I antigen processing. By engrafting shRNA tumor cell lines targeting gene candidates in immune-competent and -deficient mice, we identified that CD47, Tex9, Pex14, and Sgpl1 play putative roles in T cell-dependent recognition and elimination of EO771 tumors. CD47, a known inhibitor of target cell phagocytosis by macrophages, also regulated the adaptive immune response. Two previously understudied molecules, Pex14 and Sgpl1, appear to have immune inhibitory functions, as their respective knockdown suppressed EO771 tumor growth and increased survival of immunocompetent mice. Tex9 serves as a potential tumor antigen or immune stimulant, as reduction of expression enhances tumor growth when EO771 tumors are grown in immunocompetent mice. Therefore, this functional in vivo screening approach enabled the discovery of CD47, Pex14, Sgpl1, and Tex9 as novel tumor-based modulators of anti-tumor adaptive immunity. To the best of our knowledge, we are the first to report the successful utilization of an in vivo functional genomics approach to identify novel tumor-based mediators of immune regulation.

An authoritative panel of researchers and clinicians critically reviews the entire field to provide a comprehensive guide to modern brain tumor immunotherapy and thereby enhance future research in this area. The contributors detail many of the key laboratory experiments and clinical protocols that are currently being investigated, integrate the available information from previous and ongoing research, and help define the current status of the field. Topics range from adoptive cellular and antibody-mediated immunotherapy of brain tumors to tumor vaccines and related strategies, and include many vanguard experimental strategies and immunological techniques for studying brain tumor immunotherapy. Cutting-edge and comprehensive, Brain Tumor Immunotherapy brings together all the important recent advances in our understanding of central nervous system tumor immunology and illustrates in powerful detail the many new applications now harnessing the immune response for brain tumor therapeutics.

Dr. Judah Folkman is considered the "father of angiogenesis." Because of Folkman's discovery and research, the possibilities of angiogenic therapy have broadened beyond cancer to many noncancerous diseases. Angiogenesis: An Integrative Approach from Science to Medicine is a comprehensive, concise summary of tumor angiogenesis. It is an up-to-date and authoritative reference for the angiogenesis field as it relates to oncology. This book represents the first collection in a volume of which Folkman is co-editor. Folkman has authored nearly 400 original papers and more than 100 book chapters.