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The concept of immunologic responses against tumors is currently under intense scrutiny throughout the world. The evidence for the existence of tumor-specific transplantation antigens (TSTA) and specific immune reactions to them in experimental animals is overwhelming. The available data concerning human tumors are controversial. The reason for this is partially that antigens detectable on human tumors by in vitro assays have not been biologically characterized. In other words, we do not know if the antigens on human tumors are acting as the targets for immunologically mediated rejection processes in vivo. It was the purpose of this workshop to bring experimental tumor immunologists and clinical oncologists together in order to disclose facts and limits in tumor immunology. Clinicians were to learn how shaky the ground becomes once the experimentalist looks beyond the edge of the mouse cage. Tumor biologists heard the clinicians' urgent cry for controlled randomized trials of immunotherapy which thus reflects clearly that immunotherapy in its present form without knowledge of dose-effect-relationship does not work. Nobody would deny that the problem of human cancer smells of immunology, but since we are just about to taste it the essential ingredient might be different. In other words one might look at present rather at immunological epiphenomena than at mechanisms of tumor immul1lty operating in vivo. This problem was among others a central issue of this workshop.
Tumor immunology and immunotherapy provides a comprehensive account of cancer immunity and immunotherapy. Examining recent results, current areas of interest and the specific issues that are affecting the research and development of vaccines, this book provides insight into how these problems may be overcome as viewed by leaders in the field.
The interplay between tumors and their immunologic microenvironment is complex, difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. The present review discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment.
Immunological Surveillance
Over the past 5 years, clinical immunology, as a whole, has advanced more rapidly than over the past 20 years. Many of these advances have been que to monoclonal antibody technology with its ability to identify antigens on tumour cells with a precision never before available. Monoclonal antibodies have the ability to identify subsets of human T-Iymphocytes and aid in diagnosis of both immunodeficiency disorders such as AIDS, or autoimmune diseases, and they can be adapted as drug targeting agents. Additionally, however, major advances have been made in identifying immunomodulating agents, and the last year has seen two such agents, IL-2 and OKT3, made available commercially for such intervention. Furthermore, another immuno modulating technique, bone marrow transplantation, ha~ now been established as a curative modality in leukaemia treatment. A central issue in tumour immunology is whether human tumours express antigens which can be termed tumour-specific. This has important implications for both tumour immunity as well as drug targeting. This issue is considered in detail by R. A. Robins in the introductory chapter in which the expression of antigens in human tumours is compared with that in experimentally induced animal tumours. This controversial issue is also considered in later chapters by Bast in breast carcinoma, Riimke and de Vries in melanoma, V{mky in lung cancer, Armitage in colorectal cancer, and Paulie and Perlmann in bladder carcinoma.
Bone and soft tissue sarcomas represent only about 2% of all malignancies; however, their treatment – with the goal of curing the patient while preserving the functionality of the affected body part – can, unlike other malignancies, only be successful with therapy concepts devised by interdisciplinary teams. This volume provides an extensive up-to-date overview of the specific diagnostics and current treatment standards of these rare entities, presenting the various limb-sparing modalities for patients with bone and soft tissue sarcomas with special regard to innovative reconstructive options. The evaluation of quality of life based on validated scores and the individual methods of coping with the illness through creative artistic projects are also acknowledged and integrated in the whole concept.
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
A guide to state-of-the-art cancer immunotherapy in translational cancer research A volume in the Translational Oncology series, Immunotherapy in Translational Cancer Research explores the recent developments in the role that immunotherapy plays in the treatment of a wide range of cancers. The editors present key concepts, illustrative examples, and suggest alternative strategies in order to achieve individualized targeted therapy. Comprehensive in scope, Immunotherapy in Translational Cancer Research reviews the relevant history, current state, and the future of burgeoning cancer-fighting therapies. The book also includes critical information on drug development, clinical trials, and governmental resources and regulatory issues. Each chapter is created to feature: development of the immunotherapy; challenges that have been overcome in order to scale up and undertake clinical trials; and clinical experience and application of research. This authoritative volume is edited by a team of noted experts from MD Anderson Cancer Center, the world’s foremost cancer research and care center and: Offers a comprehensive presentation of state-of-the-art cancer immunotherapy research that accelerates the pace of clinical cancer care Filled with the concepts, examples, and approaches for developing individualized therapy Explores the breath of treatments that reflect the complexity of the immune system itself Includes contributions from a panel international experts in the field of immunotherapy Designed for physicians, medical students, scientists, pharmaceutical executives, public health and public policy government leaders and community oncologists, this essential resource offers a guide to the bidirectional interaction between laboratory and clinic immunotherapy cancer research.
Part 1: Intratumoral Signatures Associated With Immune Responsiveness
Topic Editor Dr. Lewis Shi received financial support from Varian Medical System, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.