Oncoimmunology

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.

Classically, anti-cancer therapies have always been applied with the primary aim of tumor debulking achieved through widespread induction of cancer cell death. While the role of host immune system is frequently considered as host protective in various (antigen-bearing) pathologies or infections yet in case of cancer overtime it was proposed that the host immune system either plays no role in therapeutic efficacy or plays a limited role that is therapeutically unemployable. The concept that the immune system is dispensable for the efficacy of anticancer therapies lingered on for a substantial amount of time; not only because evidence supporting the claim that anti-cancer immunity played a role were mainly contradictory, but also largely because it was considered acceptable (and sometimes still is) to test anticancer therapies in immunodeficient mice (i.e. SCID/athymic mice lacking adaptive immune system). This latter practice played a detrimental role in appreciating the role of anticancer immunity in cancer therapy. This scenario is epitomized by the fact that for a long time the very existence of cancer-associated antigens or cancer-associated ‘danger signaling’ remained controversial. However, over last several years this dogmatic view has been considerably modified. The existence of cancer-associated antigens and ‘danger signaling’ has been proven to be incontrovertible. These developments have together paved way for the establishment of the attractive concept of “immunogenic cell death” (ICD). It has been established that a restricted class of chemotherapeutics/targeted therapeutics, radiotherapy, photodynamic therapy and certain oncolytic viruses can induce a form of cancer cell death called ICD which is accompanied by spatiotemporally defined emission of danger signals. These danger signals along with other factors help cancer cells undergoing ICD to activate host innate immune cells, which in turn activate T cell-based immunity that helps eradicate live (or residual) surviving cancer cells. The emergence of ICD has been marred by some controversy. ICD has been criticized to be either experimental model or setting-specific or mostly a concept based on rodent studies that may have very limited implications for clinical application. However, in recent times it has emerged (through mainly retrospective or prognostic studies) that ICD can work in various human clinical settings hinting towards clinical applicability of ICD. However a widespread consensus on this issue is still transitional. In the current Research Topic we aimed to organize and intensify a discussion that strives to bring together the academic and clinical research community in order to provide a background to the current state-of-the-art in ICD associated bench-side research and to initiate fruitful discussions on present and future prospects of ICD translating towards the clinical, bedside reality.

Volume 1 of Dr. Jesse Stoff's "Integrative Onco-Immunology" -the first text of its kind detailing the groundbreaking approach for treating cancer patients through the support of the immune system. This book series pays homage to the complexity of the human body and recognizes that no two cancer patients are alike, either in the underlying causes of the disease or in therapeutic treatment. THE STOFF PROTOCOL of treatment brilliantly gets to the root of the problem! Once the underlying cause of the disease has been identified and reversed, the patient stands a good chance of going into remission or at least finding dramatic improvement in quality and quantity of life... Dr. Stoff leads the way toward a new healing system that's more clinically effective, more humane, and more cost effective.

Radiation Oncology and Radiotherapy, Part B, Volume 174 in the Methods in Cell Biology series, highlights advances in the field, with this new volume presenting interesting chapters on timely topics including CT-assisted focal irradiation of tumors in mice, Methods to preserve correct dosimetry in small animal irradiators, Monitoring TGFbeta signaling in irradiated tumors, Cytofluorometric characterization of the lymphoid compartment of irradiated tumors, Cytofluorometric characterization of the myeloid compartment of irradiated tumors, Mass cytometry to characterize the immune infiltrate of irradiated tumors, Characterization of the immune infiltrate in irradiated mouse tumor by multiplex immunofluorescence, and much more. Other chapters cover Methods to study FOXP3+CD8+ cells in irradiated bone metastases, Luminex-based characterization of cytokine signaling by irradiated tumors, Explant-based assessment of anticancer immunity in irradiated tumors, Pipeline to characterize the TCR repertoire of irradiated tumors, Pipeline to identify tumor neoantigens exposed by radiation, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Cell Biology series Includes the latest information on the topic of development, characterization and applications in CAR T Cells

Extracellular Vesicles, Volume 645 in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. Chapters in this new release include Genetic labeling of extracellular vesicle exosomes for studying biogenesis and uptake in living mammalian cells, Fluorescent Labeling of Extracellular Vesicles, Isolation of extracellular vesicles from lymph, Transgenic rats for tracking body fluid/tissue-derived extracellular vesicles, Isolation of amniotic extracellular vesicles, Urinary extracellular vesicle isolation, Immunocapture-based ELISA to Characterize and Quantify Extracellular Vesicles in Both Cell Culture Supernatants and Body Fluids, and much more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series

Toll-like receptors (TLRs) represent a powerful system for recognition and elimination of pathogen-associated molecular patterns (PAMPs) from bacteria, viruses, and other pathogens and damage-associated molecular patterns (DAMPs) released from dying cells. TLRs are mainly expressed on immune cells, but can also be present on other cell populations. Typical PAMPs include bacterial cell wall components, viral pathogens, or pathogenic nucleic acids, including viral RNA and DNA. Activation of TLRs leads to the production of proinflammatory cytokines and type I interferons which are important for induction of the host immune response against bacterial and viral infections. However, dysregulation and overstimulation can be detrimental leading to hyper-inflammation, sepsis, and loss of tissue integrity. Furthermore, TLRs are involved in the pathogenesis of acute viral infections, including COVID-19. Consequently, TLRs are promising targets for pharmacological intervention and treatment.

Existing culture systems have a limited ability to reproduce the complicated and dynamic microenvironment of a functioning organ. To solve the issues of conventional culture techniques, multidisciplinary researchers, involving medical doctors, stem cell and developmental biology experts, engineers and physical scientists, have emerged to innovate methods and devices. A microfluidic organ-on-a-chip (μOOC) is a cell culture device, based on microfluidic technology, which contains continuously perfused chambers with cells to simulate organ-level physiology/pathology. The μOOC is not to build a whole living organ, but rather to synthesize minimal functional units that recapitulate organ-/tissue-level functions. The μOOC can be applied to study not only the convention stimulation on cells by molecular/drugs, but also physical forces (fluid shear stress, cyclic strain and mechanical compression), organ-specific cell-cell intercommunication, and organ-organ coupling responses. There is an emerging need for innovative approaches for the production, control, analysis, and utilization of the μOOC, and even the multiple interconnected μOOC (Human-on-a-Chip). Although the μOOC has attracted much attention and is continuous being studied, there are still many difficult problems to be solved. Some of the most mentioned challenges include microenvironmental (biochemical, biophysical, biomechanical, nutrient, etc.) control, modeling tissue–tissue and multiorgan interactions, and reducing variability (automated control, high-throughput manipulation/analysis, integration of biosensing and etc.).

Radiation Oncology and Radiotherapy, Part A, Volume 172 in the Methods in Cell Biology series, highlights advances in the field, with this new volume presenting interesting chapters on timely topics, including DNA damage quantification by the COMET assay, Immunofluorescence microscopy-assisted quantification of ATM and ATR activation in irradiated cells, Immunoblotting-based characterization of the DNA damage response, Assessment of lipid peroxidation in irradiated cells, A simple method to assess clonogenic survival of irradiated cancer cells, Quantification of beta-galactosidase activity as a marker of radiation-driven cellular senescence, Cytofluorometric assessment of cell cycle progression in irradiated cells, and more. Other sections cover Assessment of transcription inhibition as a characteristic of immunogenic cell death, Assessment of eIF2a phosphorylation during immunogenic cell death, Quantification of cytosolic DNA species by immunofluorescence and automated image analysis, Flow cytometry-assisted quantification of CALR exposure during immunogenic cell death, Interference of immunogenic anticancer therapy by artificially controlled calreticulin secretion from tumor cells, along with many additional topics of interest. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Cell Biology series Includes the latest information on the topic of development, characterization and applications in CAR T Cells