Download or read book Defining the Immune Microenvironment in Sarcoma written by Marie Kostine and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Local control with adequate surgery is the cornerstone of sarcoma treatment. However, most sarcoma lack effective systemic therapies in case of advanced disease, emphasizing an unmet medical need for new therapeutic targets. The recent success of immunotherapy in epithelial malignancies raises the question whether such therapies, and which ones, would be applicable in sarcomas. As a prerequisite for therapeutic applications, we characterized the immune microenvironment in three sarcoma subtypes potentially candidate to immunotherapy: 1) In chondrosarcoma, PD-L1 expression was exclusively found in nearly 50% of the dedifferentiated subtype, in association with immune-infiltrating cells and HLA class I expression. These data provide rationale for including such patients in clinical trials with PD-1/PD-L1-targeted therapies. 2) In osteosarcoma, we observed a high density of tumor-infiltrating T cells in metastatic lesions compared to primary tumors and local relapses. Furthermore, PD-L1 positivity in almost half of metastases while mainly negative in the associated primary tumors, emphasises the dynamics of an adaptive mechanism of immune escape. Enhancing the preexisting immune response in metastatic lesions using T-cell-based immunotherapy may offer clinical benefit. 3) In leiomyosarcoma, HLA class I molecules were strongly upregulated and PD-L1 expression found in 30% of high-grade tumors, which were also highly infiltrated with CD163+ immunosuppressive macrophages. CD163+ was found to be an independent poor prognostic factor for overall survival, indicating the need for assessing a macrophage-targeted approach in this tumor type, as single agent or in combination with anti PD-1/PD-L1agents.
Download or read book Immunotherapy of Sarcoma written by Sandra P. D'Angelo and published by Springer. This book was released on 2018-11-27 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes recent progress in the development of immunotherapies for advanced sarcoma, paying special attention to the potential role of manipulations of the sarcoma tumor immune microenvironment in improving patient outcomes. Readers will find a thorough overview of the state of the art in tumor immunology and immunotherapy as they relate to sarcoma. Among the topics addressed are advances in vaccine therapy; cytokine therapies; natural killer cells; the development of adoptive T cell strategies; and the scope for use of checkpoint inhibitors in patients with sarcoma, mirroring the tremendous breakthroughs made in other malignancies. Detailed information is provided on laboratory and clinical research, with analysis of outcomes of recent trials and identification of key challenges. There is every reason to believe that more effective and less toxic therapies for metastatic sarcoma can be attained by deepening our understanding of cancer immunology and building on the advances in immunotherapy for other solid tumors. In this context, Immunotherapy of Sarcoma will be of high interest for all medical oncologists responsible for the treatment of sarcoma patients.
Download or read book Characterizing the Transcriptomic and Genomic Signatures of Immune Cell Infiltration in Undifferentiated Sarcoma written by Danielle Schwarzbein Graham and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is a critical need for more effective systemic therapies for the treatment of soft tissue sarcoma and, specifically, undifferentiated sarcoma. Immunotherapy has shown signs of efficacy for the treatment of soft tissue sarcoma, particularly in undifferentiated sarcoma, though selecting the patients who will benefit from immunotherapy remains difficult and unclear. Further studies are needed to characterize the immune landscape of soft tissue sarcoma and to develop strategies to identify patients that are likely to benefit from immunotherapy. In this study, I investigated the immunologic heterogeneity and identify transcriptomic and genomic correlates of immune cell infiltration in undifferentiated sarcoma. In doing so, I determined the immune cell landscape, the optimal high-throughput tools, and the transcriptomic and genomic changes associated with high and low immune cell infiltration in soft tissue sarcoma. This study synthesized many datasets and data types for a comprehensive analysis of the immune landscape in soft tissue sarcoma. I first characterized the immune cell landscape in soft tissue sarcoma using flow cytometry data from fresh operative samples (n=105) of multiple soft tissue sarcoma subtypes. I then generated a tissue microarray with matched RNA sequencing data from 60 samples of untreated undifferentiated sarcoma to determine the optimal method of in-silico immune deconvolution, which allows for the expansion of this analysis to other next generation sequencing data. Finally, I synthesized multiple publicly available datasets containing next generation sequencing data (RNA sequencing and whole exome sequencing) from undifferentiated sarcoma samples. This data is combined with data from the aforementioned samples for a total of 193 samples and is used to determine the transcriptomic and genomic correlates of immune cell infiltration in undifferentiated sarcoma. In the analysis of the flow cytometry data, I found that undifferentiated sarcoma tumors are characterized by a myeloid predominance and a relative abundance of suppressor cells, such as Treg cells and CD11b cells. I additionally found that the immune composition of peripheral blood was associated with intratumoral leukocyte infiltration, and specifically that myeloid-predominant tumor and lymphocyte-predominant blood are mutually exclusive. I then determined the optimal in-silico immune deconvolution tool in undifferentiated sarcoma by determining the correlation between mIF and in-silico immune deconvolution scores. Based on these findings, I suggest the following practices when applying in-silico immune deconvolution tools to undifferentiated sarcoma: (1) Use TIMER to define overall immune cell infiltration. (2) Use MCP counter to define monocyte infiltration or use CIBERSORTx, EPIC, quanTIseq, TIMER, or xCell to define macrophage infiltration. (3) Use caution when using in-silico immune deconvolution tools to define CD8+ T cell infiltration. CIBERSORTx most accurately defines CD8+ T cell immune infiltration, however, there are still many instances when tumors with high CD8+ T cell infiltration will be missed using this technique. (4) Avoid applying in-silico immune deconvolution results to define B cell or CD4+ T cell immune infiltration. Finally, I found that increased copy number changes were associated with low immune cell infiltration in undifferentiated sarcoma. These findings were suggested in both transcriptomic and genomic analyses. Interestingly, this association between CNA and immune invasion were unique to the UPS and DDLPS subtypes of STS, but it was not seen in other subtypes of STS. The mechanisms underlying this association are not clear and warrant further study. These insights provide necessary information to understand which patients may benefit from immunotherapy and guide future studies to further the treatment of soft tissue sarcoma. These studies provide the groundwork for further investigation in this study of immune cell infiltration in soft tissue sarcoma and provide insights into how we may be able to improve outcomes in this rare and devastating disease. The mechanisms underlying these findings remain unclear and warrant further investigation. A deeper understanding of the drivers of immune cell infiltration, the unique tumor microenvironment in soft tissue sarcoma, and role that chromosomal instability plays in soft tissue sarcoma will hopefully ultimately lead to insights to new, and much-needed, treatments for this disease.
Download or read book Biomarkers in Breast Cancer written by Giampietro Gasparini and published by Springer Science & Business Media. This book was released on 2008-01-17 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.
Download or read book Treatment of Bone and Soft Tissue Sarcomas written by Per-Ulf Tunn and published by Springer Science & Business Media. This book was released on 2008-12-28 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bone and soft tissue sarcomas represent only about 2% of all malignancies; however, their treatment – with the goal of curing the patient while preserving the functionality of the affected body part – can, unlike other malignancies, only be successful with therapy concepts devised by interdisciplinary teams. This volume provides an extensive up-to-date overview of the specific diagnostics and current treatment standards of these rare entities, presenting the various limb-sparing modalities for patients with bone and soft tissue sarcomas with special regard to innovative reconstructive options. The evaluation of quality of life based on validated scores and the individual methods of coping with the illness through creative artistic projects are also acknowledged and integrated in the whole concept.
Download or read book Soft Tissue and Bone Sarcoma written by Edwin Choy and published by MDPI. This book was released on 2018-10-08 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Soft Tissue and Bone Sarcoma" that was published in Cancers
Download or read book Mechanisms of Immune Regulation written by Richard D. Granstein and published by S. Karger AG (Switzerland). This book was released on 1994 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Among the topics reviewed are T and B cell tolerance, clonal deletion, suppressor cells, mechanisms of immune privileged sites and experimental models of tumor immunity. Oral tolerance, ultraviolet radiation and photosensitized effects on immunity, allograft management, T cell vaccination and regulation of immunity with T cell epitopes are discussed from the point of view of possible therapeutic application.
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Download or read book Immune Surveillance written by Richard T. Smith and published by Elsevier. This book was released on 2012-12-02 with total page 553 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immune Surveillance deals with the issues regarding tumor immunology and surveillance, in which the central theme is all about the life span of the mammalian host that is depleted by the environment with mutagenic agents and solutions. The book is divided into six chapters. It includes discussions on the organization and modulation of cell membrane receptors, as well as the origin and expression of membrane antigens. It also covers the topics on the triggering mechanisms for and effector mechanisms activated by the cellular recognition. These topics analyze and evaluate alternatives for the recognition and destruction mechanisms in the knowledge of cell cooperation and requirements for immune recognition. A chapter provides discourse on a solution for the paradox of thriving tumors based on the demonstrable in vitro host immunity. Another discusses the generation of antibody diversity and the theory of self-tolerance. The last chapter explains the evaluation of the evidence for immune surveillance. This reference will be invaluable to those who specialize in immunology.
Download or read book Soft Tissue and Bone Tumours written by WHO Classification of Tumours Editorial Board and published by WHO Classification of Tumours. This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: PLEASE NOTE: Text has been accidentally deleted from page 54 of this book. Please refer to the corrigenda (PDF file) posted on the Stylus Publishing web site or email [email protected] for an updated, printable page. ****When not purchasing directly from the official sales agents of the WHO, especially at online bookshops, please note that there have been issues with counterfeited copies. Buy only from known sellers and if there are quality issues, please contact the seller for a refund.***** Soft Tissue and Bone Tumours is the third volume in the 5th edition of the WHO series on the classification of human tumours. This series (also known as the WHO Blue Books) is regarded as the gold standard for the diagnosis of tumours and comprises a unique synthesis of histopathological diagnosis with digital and molecular pathology. These authoritative and concise reference books provide indispensable international standards for anyone involved in the care of patients with cancer or in cancer research, underpinning individual patient treatment as well as research into all aspects of cancer causation, prevention, therapy, and education. This volume will be of particular interest to pathologists, oncologists, surgeons, and epidemiologists who manage or research soft tissue and bone tumours. Sections are included on all recognized neoplasms of the soft tissue and bone, as well as on genetic tumour syndromes affecting these sites. Since the previous edition, there have been changes based on recent molecular and genetic information, with impact on clinical practice.
Download or read book General Principles of Tumor Immunotherapy written by Howard L. Kaufman and published by Springer Science & Business Media. This book was released on 2007-10-12 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book brings together the world’s leading authorities on tumor immunology. This book describes the basic immunology principles that form the foundation of understanding how the immune system recognizes and rejects tumor cells. The role of the innate and adaptive immune responses is discussed and the implications of these responses for the design of clinical strategies to combat cancer are illustrated.
Download or read book Brain Tumor Immunotherapy written by Linda M. Liau and published by Springer Science & Business Media. This book was released on 2000-11-10 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt: An authoritative panel of researchers and clinicians critically reviews the entire field to provide a comprehensive guide to modern brain tumor immunotherapy and thereby enhance future research in this area. The contributors detail many of the key laboratory experiments and clinical protocols that are currently being investigated, integrate the available information from previous and ongoing research, and help define the current status of the field. Topics range from adoptive cellular and antibody-mediated immunotherapy of brain tumors to tumor vaccines and related strategies, and include many vanguard experimental strategies and immunological techniques for studying brain tumor immunotherapy. Cutting-edge and comprehensive, Brain Tumor Immunotherapy brings together all the important recent advances in our understanding of central nervous system tumor immunology and illustrates in powerful detail the many new applications now harnessing the immune response for brain tumor therapeutics.
Download or read book The Breakthrough written by Charles Graeber and published by Twelve. This book was released on 2018-11-13 with total page 298 pages. Available in PDF, EPUB and Kindle. Book excerpt: Follow along as this New York Times bestselling author details the astonishing scientific discovery of the code to unleashing the human immune system to fight in this "captivating and heartbreaking" book (The Wall Street Journal). For decades, scientists have puzzled over one of medicine's most confounding mysteries: Why doesn't our immune system recognize and fight cancer the way it does other diseases, like the common cold? As it turns out, the answer to that question can be traced to a series of tricks that cancer has developed to turn off normal immune responses -- tricks that scientists have only recently discovered and learned to defeat. The result is what many are calling cancer's "penicillin moment," a revolutionary discovery in our understanding of cancer and how to beat it. In The Breakthrough, New York Times bestselling author of The Good Nurse Charles Graeber guides readers through the revolutionary scientific research bringing immunotherapy out of the realm of the miraculous and into the forefront of twenty-first-century medical science. As advances in the fields of cancer research and the human immune system continue to fuel a therapeutic arms race among biotech and pharmaceutical research centers around the world, the next step -- harnessing the wealth of new information to create modern and more effective patient therapies -- is unfolding at an unprecedented pace, rapidly redefining our relationship with this all-too-human disease. Groundbreaking, riveting, and expertly told, The Breakthrough is the story of the game-changing scientific discoveries that unleash our natural ability to recognize and defeat cancer, as told through the experiences of the patients, physicians, and cancer immunotherapy researchers who are on the front lines. This is the incredible true story of the race to find a cure, a dispatch from the life-changing world of modern oncological science, and a brave new chapter in medical history.
Download or read book Tumor Microenvironments in Organs written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-06 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the tumor microenvironment in over thirty human organs, including the parathyroid gland, heart, intestine, testicles, and more. Taken alongside its companion volumes, these books update us on what we know about the different aspects of the tumor microenvironments in distinct organs as well as future directions. Tumor Microenvironments in Organs: From the Brain to the Skin – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.
Download or read book Current Advances in the Science of Osteosarcoma written by Eugenie S. Kleinerman and published by Springer Nature. This book was released on 2020-08-07 with total page 233 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thoroughly revised second edition is an up-to-date overview of the new advances in the knowledge of the basic science in sarcoma and osteosarcoma. It features detailed, in-depth discussions of microRNAs in osteosarcoma, historical perspectives of chemotherapy in the treatment of the disease, tumor targeted IL12 therapy and HER2 targeted therapy, the role of enhancer elements in regulating the prometastatic transcriptional program and more. Further, this essential volume also includes new insights on Wnt signaling in osteosarcoma, the role of genomics, genetically modified T-cell therapy, liquid biopsy, oncolytic viruses, immunophenotyping, receptor tyrosine kinases and epigenetic-focused approaches for treatment of osteosarcoma metastases, as well as thoughts on the current standard of treatment for patients suffering from these cancers. In the years since the previous edition, there have been numerous new developments in this rapidly changing field; this new edition is both timely and urgently needed. When taken together these companion volumes, Current Clinical (Book 1) and Scientific (Book 2) Advances in Osteosarcoma, are a timely and urgently needed guide for laboratory investigators and clinical oncologists.
Download or read book Immune Checkpoint Inhibitors in Cancer written by Fumito Ito and published by Elsevier Health Sciences. This book was released on 2018-09-03 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Get a quick, expert overview of the latest clinical information and guidelines for cancer checkpoint inhibitors and their implications for specific types of cancers. This practical title by Drs. Fumito Ito and Marc Ernstoff synthesizes the most up-to-date research and clinical guidance available on immune checkpoint inhibitors and presents this information in a compact, easy-to-digest resource. It’s an ideal concise reference for trainee and practicing medical oncologists, as well as those in research. Discusses the current understanding of how to best harness the immune system against different types of cancer at various stages. Helps you translate current research and literature into practical information for daily practice. Presents information logically organized by disease site. Covers tumor immunology and biology; toxicities associated with immune checkpoint inhibitors; and future outlooks. Consolidates today’s available information on this timely topic into one convenient resource.
Download or read book Comparative Oncology written by Alecsandru Ioan Baba and published by . This book was released on 2007 with total page 787 pages. Available in PDF, EPUB and Kindle. Book excerpt:
