This book reviews current immunotherapeutic strategies for gastrointestinal (GI) malignancies, including immune composition, immune checkpoint inhibitors, cell therapy, and peptide vaccines used to protect against esophageal, gastric, hepato-biliary, pancreatic and colorectal cancers. It also discusses the current challenges of using immunotherapy for the treatment of gastrointestinal malignancies. The book reviews highly sensitive and specific immunomarkers for the detection of GI malignancies, and examines therapeutic vaccines and the major cytokines involved in GI immunotherapy, as well as their basic biology and clinical applications. In closing, the book explores various aspects of computational biology for the detection and treatment of GI malignancies.

This book is about the manipulation of the immune system as a therapeutic approach to gastrointestinal cancer and its clinical applications, exploring therapeutic approaches which might be taken under the broad banner of immunotherapy. Starting by introducing concepts of modern immunology, the clinical applications of immunotherapy are then discussed. The reader will learn about the three broad classes of immune therapeutic agents: cell-based treatment; antibody therapy; cytokine application and the key effector cells and mechanisms which might cause tumour rejection. The reverse side of this equation, the genetic and molecular mechanisms which the tumour can use to escape immune control and regulation, is also discussed. Through reviewing the most up-to-date evidence, this volume provides an overview of the important scientific lessons learned from past failure of immunotherapeutics in the clinic and highlights more positive recent data, coupled to practical guidelines for clinical usage. Written by a team of worldwide experts, this is an indispensable guide for medical oncologists, surgical oncologists, radiation therapists, pharmacists, oncology nurse specialists.

Currently, the treatment options for gastrointestinal malignancies mainly include surgery, chemotherapy, radiotherapy, and molecular targeted therapy, etc. Drug therapy is one of the main treatments for patients with advanced stages, but the efficacy of chemotherapy seems to have reached a plateau, and the progress of traditional molecular targeted therapy is relatively slow. In addition, the benefits of the current chemotherapy combined with targeted therapy for patients with advanced stages of gastrointestinal malignancies are still not satisfactory. Tumor immunotherapy is an emerging therapeutic approach and is a current research hotspot, and there are hopes that immunotherapy can help further improve the prognosis and quality of life for patients with gastrointestinal malignancies. At the same time, potential targets of immunotherapeutic drugs and prognostic biomarkers for gastrointestinal malignancies have been less studied than other common cancers, such as lung cancer. Prognostic biomarker studies are the beginning of exploring new drug targets and revealing potential mechanisms of tumor progression. Immunotherapies, particularly PD1 or PD-L1 antagonists, have demonstrated effective therapeutic efficacy against various types of cancer. To date, many PD1 drugs are available for cancer treatment, and more than 100 PD1 drugs are in clinical trials. However, the question of how to screen sensitive patients and predict the efficacy of immunotherapy remains unresolved. In addition, predictive biomarkers and treatment guidelines for immunotherapy of gastrointestinal malignancies have hardly been studied.

Designed for quick, everyday reference, Handbook of Targeted Cancer Therapy and Immunotherapy: Gastrointestinal Cancer provides a practical overview of this rapidly advancing field. Comprehensive yet concise, this easy-access resource by Dr. Milind Javle of MD Anderson Cancer Center and Dr. Mitesh J. Board of Mayo Clinic helps you filter and apply the most recent discoveries as they pertain to specific tumor types, actionable molecular targets, and clinical performance of investigational targeted agents and combinations of agents.

Gastrointestinal (GI) cancers, including gastric cancer, colon cancer, liver cancer, esophageal cancer, and pancreatic cancer, seriously threaten the health of human beings worldwide with a high rate of morbidity and mortality. The clinical successes achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have opened a new cancer therapy era and brought new hope to cancer patients. However, the overall response rate (ORR) of ICI monotherapy in the non-selective population is only about 20%, in which some patients subsequently develop immunotherapy resistance. Moreover, the remaining 70-80% of patients displayed primary resistance to ICIs, and a few patients even experienced hyper progression disease (HPD). Although PD-L1 expression, mismatch repair deficient (MMRd), high tumor mutational burden (TMB-H) , high homologous recombination deficiency (HRD), and tumor infiltrated immune cells (TILs) are known as effective biomarkers for immunotherapy, growing studies have reported that ICIs could not improve the OS of all patients with PD-L1 expression higher than 50%, and the ORR of MSI-H patients was only about 60%, whereas some patients with low PD-L1 expression or MSS could still benefit from immunotherapy, indicating the complexity of ICI resistance. Therefore, it is of great importance and significance to explore the prediction biomarkers for primary or acquired immunotherapy resistance and elucidate their underlying molecular mechanisms and develop reversal strategies. Due to the multiple steps of the cancer immune cycle and complex immune microenvironment, any disorders of immune cell infiltration or T cell activation, such as lack of antigens and/or their presentation, lack of response to antigen presentation, and T cell priming, could contribute to ICI resistance. The combination with anti-angiogenesis therapy, radiotherapy, chemotherapy, and other ICIs has improved the efficacy of ICI therapy to some extent in the clinic. Although numerous studies related to ICI resistance were reported in GI cancers, due to the strong spatial/temporal heterogeneity and the complex immune microenvironment in different kinds of GI cancers and different individuals, many questions about ICI resistance and reversal strategies remain unsolved. The aim of this Research Topic is to provide a forum to exhibit the latest research achievement related to the exploration of biomarkers for immunotherapy resistance including HPD and the underlying molecular mechanisms, as well as the development of reversal strategies in GI cancers. We hope this Research Topic will lead to a better understanding of precision cancer immunotherapy and provide useful clues for clinical application to benefit more GI cancer patients with immunotherapy.

Principles of Immunotherapy in Breast and Gastrointestinal Cancers: Activity, Mechanisms of Resistance and New Sensitization Strategies presents updated research findings on immunotherapy, with special focus on the mechanisms of resistance of those cancer types and how to overcome them. The book discusses topics such as tumor cell-intrinsic and extrinsic mechanisms of cancer resistance to immunotherapy; the role of currently available biomarkers; strategies to overcome therapeutic resistance; sensitizing agents for cancer resistance to cell mediated immunotherapy; and Immunotherapeutic approaches, mechanisms of resistance and sensitizing strategies in gastroesophageal and biliopancreatic tumors and colorectal cancer. It is a valuable resource for researchers, students and members of the biomedical and medical fields who want to learn more about resistance to immunotherapy and how to overcome it. - Presents relevant findings on immunotherapy for breast and GI cancer types in a synthetic and didactic way for easy consult - Describes resistance mechanisms of those cancer types and how to overcome them to improve immunotherapy outcomes - Encompasses several diagrams and figures to help readers get a clearer picture of the research findings and how they can be applied to the clinical setting

The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.