Download or read book Characterizing the Tumor Microenvironment Upon Transcutaneous Immunization by Single cell RNA sequencing Implications for Cancer Immunotherapy written by Joschka Matthias Bartneck and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The treatment of cancer diseases is one of the greatest challenges for modern medicine. In addition to conventional cancer therapy approaches, cancer immunotherapy has been gaining importance for more than two decades. In this context, the use of cancer vaccines that induce the formation of high-quality tumor-specific T cells is a promising tool that is now being intensively researched. Therapeutic approaches are needed that specifically sensitize the host immune system to the tumor and are able to specifically address targets in the complex immune-inhibitory network of the tumor microenvironment, a major obstacle affecting the efficiency of immunotherapeutic approaches. The transcutaneous immunization method developed in the research group of Prof. Dr. Markus Radsak enables the generation of antigen-specific CD8+ and CD4+ T cells by activating skin tissue-resident antigen-presenting cells. With the aim of first optimizing the memory T cell response, the frequency of antigen-specific activated T cells was massively increased in the present work by multiple TCI. The optimized Dithranol-Imiquimod-based transcutaneous immunization (DIVA2) enabled protection against MC38mOVA tumor cells in a prophylactic tumor setting. Applied in a therapeutic Tumor setting, DIVA2 resulted in transient tumor immune control. High-dimensional flow cytometry analysis and single-cell mRNA-sequencing of tumor-infiltrating leukocytes showed that DIVA2-induced cytotoxic CD8+ T cells facilitate initial tumor immune control, but are inhibited by immunosuppressive CCR2+ PD L1+ monocyte-derived myeloid-derived suppressor cells (M-MDSC), resulting in partial T-cell exhaustion. Furthermore, CD38 expression by macrophages during immune control implicated production of the immunosuppressive adenosine. Anti-CCR2 antibody-based depletion of CCR2+ monocytes in the tumor experiment highlighted their immunosuppressive nature, but could not persistently limit tumor growth as depletion could not be continuously ensured. The use of the immune checkpoint inhibitor anti-PD-1 enabled a strong regression of the tumors in a therapeutic tumor setting, which illustrates the immunosuppressive role of the PD-1/PD-L1 axis in the tumor microenvironment of MC38mOVA tumors after initial DIVA2-induced immune control. In summary, the present work provides a platform for generating a strong antigen-specific primary and memory T cell immune response using the optimized transcutaneous immunization method DIVA2. This enables protection against tumor cells and transient therapeutic immune control of solid tumors. For a successful therapeutic elimination of tumors, the identification of specific immune targets is necessary.

Download or read book Single cell Methods for Profiling Tumor Microenvironment Responses to Therapeutic Challenges written by Sanjay Mathews Prakadan and published by . This book was released on 2020 with total page 177 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heterogeneity among cells affects function and dysfunction across many complex biological systems. This heterogeneity is particularly important in cancer biology, where variation in the cells composing tumors and their surroundings can affect a patients' response to treatment and subsequent survival. While current methods, such as bulk RNA-Sequencing, are incredibly powerful, they typically measure average phenomena, mischaracterizing the distribution of behaviors within a system. Single-cell technologies - single-cell RNA Sequencing in particular have been foundational in elucidating cellular heterogeneity from first principles, but there are limitations to their application for studying cancer and its response to treatment. Here, we detail efforts to address current needs in profiling treatment responses of tumors and their microenvironments at single-cell resolution. Specifically, we characterize the underlying cellular diversity of tumor microenvironments, investigate the effect of drug treatment in specific cellular compartments, identify proxies of response in accessible cellular reservoirs, and investigate orthogonal cellular readouts of response. We first apply single-cell RNA Sequencing to study heterogeneity in metastatic melanoma, detailing heterogeneity and potential sources of resistance in cancer cells of profiled patients. Next, we study the effect of drug treatment in leptomeningeal carcinomatosis (LMD), extending previous strategies to utilize pre- and post-treatment patient sampling. We demonstrate the effect of immunotherapy in this microenvironment, and use longitudinal data from specific patients describe the evolution of cancer cell response to treatment. We next expand liquid biopsy profiling to other compartments, specifically circulating tumor cells (CTCs) in blood. We describe the development of a microfluidic device that captures murine CTCs with minimal sampling. We perform single-CTC RNA-Sequencing to study their response to treatment and relationship to their primary tumors. Finally, we develop a device that simultaneously measures the mass, growth rate and transcriptome of single cells, and use it to investigate the transcriptional activity of cancer cells that continue to grow after therapeutic challenge. Together, this body of work represents contributions towards extending single-cell profiling to understand how cells in naturally occurring and model cancer microenvironments respond to drug treatment.

Download or read book Immunotherapy of Hepatocellular Carcinoma written by Tim F. Greten and published by Springer. This book was released on 2018-08-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.

Download or read book Understanding convergent evasion mechanisms in cancer and chronic infection Implications for immunotherapy written by Matthias Theobald and published by Frontiers Media SA. This book was released on 2024-06-04 with total page 247 pages. Available in PDF, EPUB and Kindle. Book excerpt: The complex interactions between the innate and adaptive immune systems function to recognize and clear pathogens or transformed cells, but inefficient interactions between these two systems can result in harmful immunologic responses including chronic infections and the development of cancer. Several hallmarks of dysfunctional adaptive immune responses often detected in tumors share specific features with ineffective immunity in chronic infections. The members of the micromilieu actively participate in the process of tumorigenesis or chronification of infection by modulating innate and adaptive immune system interactions leading e.g. to insufficient T cell responses. The best example is given by the acquisition of an “exhausted” state of cytotoxic CD8+ T cells (CTLs) responding to chronic infections or tumors that are associated with elevated expression of inhibitory receptors and impaired cytokine response. Targeting these major inhibitory pathways by immune checkpoint blockers represents a prime example of successful clinical translation of tumor-specific immunotherapies. Understanding the mechanisms behind (mal)adaptations of the immune system is crucial for achieving therapeutic benefits. The establishment and co-evolution of a dynamic microenvironment niche constituted by the recruitment of numerous cell types dampen immune responses and thus contribute to the development of neoplastic transformation as well as infection. Although there are examples of successful immunotherapeutic approaches (CAR-T cells, immune checkpoint inhibitors, or mRNA vaccination), a large percentage of patients with cancer or chronic infections still do not benefit from these therapies or develop severe immune-related adverse events. The reasons for these failures are not well understood. A possible explanation might be that current immunotherapies target predominantly the effector arm of the immune system by trying to reactivate dysfunctional T cells, but do not sufficiently address the influence of the innate immune system and the contributions of the tumor microenvironment (TME) niche. The main problem we would like to address in this special issue is how inappropriate function of the innate immune system affects adaptive immunity and contributes to inefficient anti-cancer immunity and chronification of infections. The central goal is to provide a more precise understanding of the various (common and novel) immune evasion mechanisms in cancers and in chronic infections to obtain a detailed map of common and disease-specific immune escape checkpoints. To that aim, we want to compile a wide array of interdisciplinary studies exploring a comparative and multi-layered analysis of mechanisms responsible for inefficient immune responses, including novel approaches i.e. multi-omics or epigenetic signaling. We would also like to combine studies from different fields, including basic and clinical immunology, oncology, and virology/microbiology. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case report, and Perspective articles that cover, but are not limited to the following topics: • Convergent mechanisms supporting immune escape in preclinical models (tumors and chronic infections) • Convergent evasion mechanisms mediated by tumor-infiltrating suppressive cells (Treg, MDSC, macro-phages, soluble mediators, signaling, metabolism, ...) • Convergent immune evasion mechanisms mediated by chronic infection (viral or parasite) • Novel strategies to modulate the TME by direct or indirect targeting of immune suppressor cells. • Approaches to enhance persistence and resilience of anticancer T cells • Combinatorial therapeutic strategies (mRNA, antibodies, immune checkpoint blockers …) that target convergent immune evasion mechanisms Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

Download or read book Angiogenesis Assays written by Carolyn A. Staton and published by John Wiley & Sons. This book was released on 2007-01-11 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.

Download or read book Tertiary Lymphoid Structures written by Marie-Caroline Dieu-Nosjean and published by Humana Press. This book was released on 2018-09-05 with total page 289 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.

Download or read book Advanced Healthcare Materials written by Ashutosh Tiwari and published by John Wiley & Sons. This book was released on 2014-05-09 with total page 421 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers

Download or read book Melanoma Development written by Anja K. Bosserhoff and published by Springer. This book was released on 2018-07-15 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on malignant melanoma, discussing the current state of scientific knowledge and providing insights into the underlying basic mechanisms, the molecular changes, genetics and genomics. Human Melanoma is a dangerous type of skin cancer affecting an increasing population, and a better understanding of its development will help in finding sophisticated targeted therapies. The second revised edition features the latest research findings and offers updates on the latest advances and potential novel melanoma therapies. It is a valuable resource for researchers and clinicians working in the fields of melanoma, cancer research and therapy as well as dermatology.

Download or read book Radiomics and Radiogenomics written by Ruijiang Li and published by CRC Press. This book was released on 2019-07-09 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: Radiomics and Radiogenomics: Technical Basis and Clinical Applications provides a first summary of the overlapping fields of radiomics and radiogenomics, showcasing how they are being used to evaluate disease characteristics and correlate with treatment response and patient prognosis. It explains the fundamental principles, technical bases, and clinical applications with a focus on oncology. The book’s expert authors present computational approaches for extracting imaging features that help to detect and characterize disease tissues for improving diagnosis, prognosis, and evaluation of therapy response. This book is intended for audiences including imaging scientists, medical physicists, as well as medical professionals and specialists such as diagnostic radiologists, radiation oncologists, and medical oncologists. Features Provides a first complete overview of the technical underpinnings and clinical applications of radiomics and radiogenomics Shows how they are improving diagnostic and prognostic decisions with greater efficacy Discusses the image informatics, quantitative imaging, feature extraction, predictive modeling, software tools, and other key areas Covers applications in oncology and beyond, covering all major disease sites in separate chapters Includes an introduction to basic principles and discussion of emerging research directions with a roadmap to clinical translation

Download or read book Phenotypic Switching written by Herbert Levine and published by Academic Press. This book was released on 2020-06-10 with total page 773 pages. Available in PDF, EPUB and Kindle. Book excerpt: Phenotypic Switching: Implications in Biology and Medicine provides a comprehensive examination of phenotypic switching across biological systems, including underlying mechanisms, evolutionary significance, and its role in biomedical science. Contributions from international leaders discuss conceptual and theoretical aspects of phenotypic plasticity, its influence over biological development, differentiation, biodiversity, and potential applications in cancer therapy, regenerative medicine and stem cell therapy, among other treatments. Chapters discuss fundamental mechanisms of phenotypic switching, including transition states, cell fate decisions, epigenetic factors, stochasticity, protein-based inheritance, specific areas of human development and disease relevance, phenotypic plasticity in melanoma, prostate cancer, breast cancer, non-genetic heterogeneity in cancer, hepatitis C, and more. This book is essential for active researchers, basic and translational scientists, clinicians, postgraduates and students in genetics, human genomics, pathology, bioinformatics, developmental biology, evolutionary biology and adaptive opportunities in yeast. Thoroughly addresses the conceptual, experimental and translational aspects that underlie phenotypic plasticity Emphasizes quantitative approaches, nonlinear dynamics, mechanistic insights and key methodologies to advance phenotypic plasticity studies Features a diverse range of chapter contributions from international leaders in the field

Download or read book Multi Drug Resistance in Cancer written by Jun Zhou and published by Humana Press. This book was released on 2012-08-09 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .

Download or read book Textbook of Oral Cancer written by Saman Warnakulasuriya and published by Springer Nature. This book was released on 2020-02-22 with total page 449 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive multidisciplinary book examines all aspects of cancers of the mouth and oropharynx with the aim of equipping advanced students and practitioners in the early stages of specialist training with an up-to-date guide and reference. A multinational team of authors – all experts in the field of oral oncology – provide illuminating contributions on the full range of relevant topics: epidemiology, risk factors, clinical features, staging and prognostic factors, pathology, diagnostic techniques, disease prevention, surgery, radiotherapy, and chemotherapy. Molecular biology, molecular targeted therapies for advanced cases, and future diagnostic and prognostic applications of new technologies also receive careful attention. In providing a wealth of essential information and guidance in a practical format, the book will be a superb asset for senior graduate students in dentistry and specialist trainees in head and neck oncology. It will also be of high value for the many physicians, surgeons, pathologists, dentists, and specialists involved in the prevention, diagnosis, and management of squamous cell carcinomas of the oral cavity and oropharynx.

Download or read book Immunopharmacology written by Manzoor M. Khan and published by Springer Science & Business Media. This book was released on 2008-12-19 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the past decades, with the introduction of the recombinant DNA, hybridoma and transgenic technologies there has been an exponential evolution in understanding the pathogenesis, diagnosis and treatment of a large number of human diseases. The technologies are evident with the development of cytokines and monoclonal antibodies as therapeutic agents and the techniques used in gene therapy. Immunopharmacology is that area of biomedical sciences where immunology, pharmacology and pathology overlap. It concerns the pharmacological approach to the immune response in physiological as well as pathological events. This goals and objectives of this textbook are to emphasize the developments in immunology and pharmacology as they relate to the modulation of immune response. The information includes the pharmacology of cytokines, monoclonal antibodies, mechanism of action of immune-suppressive agents and their relevance in tissue transplantation, therapeutic strategies for the treatment of AIDS and the techniques employed in gene therapy. The book is intended for health care professional students and graduate students in pharmacology and immunology.

Download or read book Hyperthermia In Cancer Treatment A Primer written by Gian F. Baronzio and published by Springer Science & Business Media. This book was released on 2008-05-08 with total page 382 pages. Available in PDF, EPUB and Kindle. Book excerpt: Following an introductory overview, Hyperthermia In Cancer Treatment: A Primer comprehensively describes the biological reasons for associating hyperthermia with radiation and chemotherapy and the biological and clinical effects of hyperthermia on cancerous and normal tissues. The volume’s 20 chapters are arranged in three principal parts: physical and methodological studies, biologic principles, and clinical studies.

Download or read book Industrial Pharmaceutical Biotechnology written by Heinrich Klefenz and published by Wiley-VCH. This book was released on 2002-04-22 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on pharmaceutical biotechnology as a key area of life sciences. The complete range of concepts, processes and technologies of biotechnology is applied in modern industrial pharmaceutical research, development and production. The results of genome sequencing and studies of biological-genetic function are combined with chemical, micro-electronic and microsystem technology to produce medical devices and diagnostic biochips. A multitude of biologically active molecules is expanded by additional novel structures created with newly arranged gene clusters and bio-catalytic chemical processes. New organisational structures in the co-operation of institutes, companies and networks enable faster knowledge and product development and immediate application of the results of research and process development. This book is the ideal source of information for scientists and engineers in research and development, for decision-makers in biotech, pharma and chemical corporations, as well as for research institutes, but also for founders of biotech companies and people working for venture capital corporations.