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.

In this book, leading experts in cancer immunotherapy join forces to provide a comprehensive guide that sets out the main principles of oncoimmunology and examines the latest advances and their implications for clinical practice, focusing in particular on drugs with FDA/EMA approvals and breakthrough status. The aim is to deliver a landmark educational tool that will serve as the definitive reference for MD and PhD students while also meeting the needs of established researchers and healthcare professionals. Immunotherapy-based approaches are now inducing long-lasting clinical responses across multiple histological types of neoplasia, in previously difficult-to-treat metastatic cancers. The future challenges for oncologists are to understand and exploit the cellular and molecular components of complex immune networks, to optimize combinatorial regimens, to avoid immune-related side effects, and to plan immunomonitoring studies for biomarker discovery. The editors hope that this book will guide future and established health professionals toward the effective application of cancer immunology and immunotherapy and contribute significantly to further progress in the field.

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.

Most cancer deaths are a result of metastasis. The spread of a primary tumor to colonize neighboring and distant organs is the relentless endgame that defines the neoplastic process. Patients who have been diagnosed with cancer are treated to prevent both the recurrence of the tumor at the site of origin and metastasis that would re-stage them as advanced stage IV cancer. Historically and still with some types of cancer, stage IV is perceived by patients as “terminal.” Fortunately, recent molecular therapies have extended the lives of patients with advanced cancer and reassuringly people living with metastatic disease increasingly visit our clinics. What is the path forward? Given that the consilience of science and medicine is a dynamic art from which therapies arise, it would be misguided to consider any single work adequate at capturing the horizon for research. So with humility we constructed this text as primer for scientists. It begins with a broad introduction to the clinical management of common cancers. This is intended to serve as a foundation for investigators to consider when developing basic science hypotheses. Unquestionably, medical and surgical care of cancer patients reveals biology and dictates how novel therapeutics will ultimately be evaluated in clinical trials. The second section of this text offers provocative and evolving insights that underscore the breadth of science involved in the elucidation of cancer metastasis biology. The text concludes with information that integrates scientific and clinical foundations to highlight translational research. This book serves as a framework for scientists to conceptualize clinical and translational knowledge on the complexity of disease that is metastatic cancer.

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.

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

This book is about the escape strategies used by cancer cells to avoid the immune response of the host. The main characters of this story are the “Antigen Presenting Molecules” and the “T Lymphocytes”. The former are known as the Major Histocompatibility Complex (MHC): the H-2 and the HLA molecules. The latter are a subgroup of white cells travelling all over our body which are capable to distinguish between “self and non self”. Readers will know from the inside about the history of the HLA genetic system and will discover how T lymphocytes recognize and destroy cancer cells. One of the key important questions is: Why tumors arise, develop and metastasize? This book tries to answer this question and will explain how cancer cells become invisible to killer T lymphocytes. The loss of the HLA molecules is a major player in this tumor escape mechanism. Cancer immunotherapy is aimed at stimulating T lymphocytes to destroy tumor cells. However, the clinical response rate is not as high as expected. The molecular mechanisms responsible for MHC/HLA antigen loss play a crucial role in this resistance to immunotherapy. This immune escape mechanism will be discussed in different types of tumors: lung, prostate, bladder and breast...ect. as well as melanoma and lymphoma. This book will be useful to Oncologists, Pathologists and Immunologist that will enter this fascinating area of research. It will be also interesting for biologist, doctoral students and medical residents interested in “Tumor Immunology”.