Breaking Tolerance To Unresponsiveness To Immunotherapy By Natural Killer Cells

Breaking Tolerance to Unresponsiveness to Immunotherapy by Natural Killer Cells presents chapters by leaders in translational natural killer cell research and bridges the gap between clinical need and basic science by presenting state-of-the-art knowledge on innate immunity and the challenges associated with translating it to practical adoptive immunotherapies. New approaches, such as the genetic engineering of NK cells and their combination with checkpoint blockade therapies are discussed among other potential interventions to improve natural killer cell functionality against targets. In addition, challenges, such as the difficulty in genetically modifying NK cells or a poor understanding of their effect on checkpoint inhibition are included. The book is a key reference and go-to resource for researchers and clinicians who want to understand the current limitations associated with bringing natural killer cell-based immunotherapies to the clinic. Discusses translational aspects from leaders in the field to facilitate readers' understanding of clinical challenges Addresses important events that occur in patient tumor microenvironments as they pertain to NK cells and how they are, or can be, tackled to overcome immunosuppression of NK cells Focuses on immunometabolism by discussing the metabolic reprogramming that NK cells undergo in solid tumors, including hypoxia, adenosine and other metabolites

NK Cells in Cancer Immunotherapy: Successes and Challenges explains the latest immunotherapeutic strategies, focusing on NK cells to allow the best and precise combination treatments to cancer patients. The book provides existing background knowledge in the field of immunotherapy and discusses future areas of research required to carry out cutting-edge, validated therapies. Chapters cover advances in immunotherapeutic strategies, in particular, the use of NK cells with and without T-cell therapy in the treatment of cancer. The book is a valuable resource for cancer researchers, oncologists, graduate students and those interested in learning more about novel strategies to treat cancer patients. Immunotherapy is fast becoming the method of choice for cancer therapy. Although remarkable advances have been made in the field of immunotherapy, there are significant challenges and difficulties ahead since many of the current immunotherapeutic strategies do not provide long-lasting treatment strategies, and therefore are not very effective. Covers CAR/T and CAR/NK and adoptive NK cell therapy with and without T cell therapies Discusses basic biology of NK cells and mouse models of human cancers and the role of NK cells in metastatic cancer and in cancer stem cells Encompasses information on combination therapies using check point inhibition, adoptive transfer of cytotoxic effector cells, chemotherapeutic drugs and activating and inhibitory antibodies

Immunotherapeutic Strategies for the Treatment of Glioma provides a review of the current state of immunotherapy for primary brain tumors. The topic is of interest to patients, clinicians, and researchers alike, particularly given the recent failure of large clinical trials. This book serves as an overview of the most promising approaches in the field and provides a foundation for considering novel and combination therapies moving forward. The book discusses several types of immunotherapies for glioma, such as peptide, dendritic cell and heat shock protein vaccines; immune checkpoint blockade; myeloid cells as target; oncolytic viruses; and CAR T cell therapy. Additionally, it discusses the mechanisms of immune suppression in patients and immunogenomics. This volume is a valuable source for cancer researchers, oncologists and several members of biomedical field who are interested in novel strategies to fight glioblastoma. Summarizes the work in immunotherapy for glioma to-date, including the available evidence from preclinical studies and clinical trials Reviews the challenges and successes of the most promising strategies for brain tumor immunotherapy Provides a foundation for considering novel and combination therapies moving forward

Immunotherapy in Resistant Cancer: From the Lab Bench Work to Its Clinical Perspectives provides high level knowledge on detailed mechanisms of actions and biological interactions of different immune drugs, with an aim of offering researchers and clinicians cutting-edge therapies to overcome drug resistance. The book explains the latest immunotherapies for different types of cancer, helping users carry out research projects or create alternatives for drug development in the pharmaceutical industry. Topics discussed include the relationship between immunotherapy and macrophages, immune checkpoints in different types of cancer, immune cocktails in solid tumors, and immune-phenotyping. Additionally, the book presents basic and clinical data on immunoresistance and glycosylation. This book is a valuable source for cancer researchers, medical doctors, clinicians and members of the biomedical field who must understand certain mechanisms to fight cancer that is resistant to immunotherapy. Provides basic and clinical evidence based on molecular interactions and clinical studies to address the risks and benefits of cancer immunotherapy Presents the results of new immunotherapy trials, discussing the state-of-the-art in different types of cancer Discusses targeted therapies approved by the FDA, along with therapies with clinical potential used in basic studies

Improving the Therapeutic Ratio in Head and Neck Cancer provides a complete review of current approaches to modulating therapeutic sensitivity in head and neck cancer. It presents a broad background of current approaches and by highlighting the potential for clinical translational, introduces a roadmap for how to move promising preclinical findings into the clinic. The book discusses topics such as immunotherapy and molecularly targeted therapies in head and neck cancer, PI3k/mTOR pathway, autophagy inhibition to sensitize HNC to radiation and chemotherapy, TAM and Eph/Ephrin family proteins and metabolic reprogramming to modulate therapeutic sensitivity. Additionally, it details approaches to improve the response to immunotherapy, and Chk1/2 inhibition in radiation and cetuximab resistance. This book is a valuable source to head and neck cancer researchers and advanced students, and to those studying specific approaches in other model systems and disease sites. Provides key scientific background for clinicians when developing novel clinical trials and important examples for basic scientists of the types of work required to move a concept from the lab to the clinic Presents consistent pathway diagrams in each chapter, thus making it easier to understand complicated pathways Includes chapter summaries of the critical next steps needed to move studies from their current state into practice changing clinical data

Successes and Challenges of NK Immunotherapy: Increasing Anti-tumor Efficacy describes the unique therapeutic applications of NK cells to fight cancers and eliminate the bulk and subset of cancer stem cells responsible for metastasis, relapse and recurrences. The book provides information on the development, engineering, mechanisms of action, response to various preclinical models, and applications in various clinical trials. Sections cover the development of highly engineered cytotoxic NK cells, their mechanisms of action, preclinical and clinical applications, the development and application of CAR-NK cells, and new NK-drug conjugates, also emphasizing that activated NK cells can target and kill highly resistant cancer stem cells. Written by the leading experts on NK immunotherapy worldwide, this is a valuable resource for researchers, clinicians and members of the biomedical field who are interested in understanding novel and efficient therapies to fight cancers. Discusses the unique developmental applications of NK immunotherapy against cancers, which differs greatly from other types of immunotherapies Provides up-to-date and highly relevant information through chapters written by the leading researchers in the field Presents a significant number of schematic diagrams for easy understanding and reproducibility

Leading investigators and clinicians detail the different mechanisms used by tumors to escape and impair the immune system and then spell out possible clinical strategies to prevent or reverse tumor-induced immune dysfunction. The authors review the mechanisms of immune dysfunction and evasion mechanisms in histologically diverse human tumors, focusing on tumor-induced molecular defects in T cells and antigen-presenting cells (dendritic cells and tumors), that may serve as biomarkers for patient prognosis. They discuss the means by which these immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques are outlined with the capacity to monitor the strength and quality of patients' immune responses using immunocytometry, MHC-peptide tetramers combined with apoptosis assay, ELISPOT assay, and detection of MHC-TAA peptide complexes on tumor cells.

In 1960 Sir Frank Macfarlane Burnet received the Noble Prize in Physiology and Medicine. He titled his Nobel Lecture “Immunological Recognition of Self” emphasizing the central argument of immunological tolerance in “How does the vertebrate organism recognize self from nonself in this the immunological sense—and how did the capacity evolve.” The concept of self is linked to the concept of biological self identity. All organisms, from bacteria to higher animals, possess recognition systems to defend themselves from nonself. Even in the context of the limited number of metazoan phyla that have been studied in detail, we can now describe many of the alternative mechanism of immune recognition that have emerged at varying points in phylogeny. Two different arms—the innate and adaptive immune system—have emerged at different moments in evolution, and they are conceptually different. The ultimate goals of immune biology include reconstructing the molecular networks underlying immune processes.