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This book provides the immune oncology (IO) community with a deeper understanding of the scope of the biomarker methods to potentially improve the outcome from immunotherapy. The editors secured the input from experts in the field dedicated to translating scientific research from bench to bedside was submitted. The book provides not only details about the technical, standardization and interpretation aspects of the methods but also introduces the reader to the background information and scientific justification for selected biomarkers and assays. 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.
Immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-PD-L1 antibodies are highly effective against many types of cancer, yet durable responses are limited to a subset of patients highlighting the need for the development of effective biomarkers to predict prognosis and efficacy. Currently, PD-L1 expression in tumors, microsatellite instability (MSI) or mismatch repair deficiency (dMMR), and tumor mutation burden (TMB) are known as biomarkers for cancer immunotherapy but are not sufficient. Combination therapy with immune checkpoint inhibitors and chemotherapy or radiation therapy, as well as diverse therapies targeting intra-tumoral regulatory T cells have been described, but there are currently no unifying biomarkers that are applicable to clinically, a simple, fast, non-invasive method that can yield biomarkers of disease with a minimal adverse effect on patients is desirable. Recent findings suggest that the balancing of effector T cells and regulatory cells in the tumor microenvironment is associated with cancer progression and prognosis. Cells and molecules involved in the control of cancer are complex, and a better understanding of the tumor immune environment will lead to the development of truly effective biomarkers. This topic will focus on novel biomarkers that predict efficacy, prognosis, or the development of adverse events in various cancer immunotherapies, and extensive basic research leading to the development of biomarkers. 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. We expect a wide range of research, not only in serology, genetics, and immunocytochemistry but also in bacterial flora. Research on the development of novel assays and bioinformatics methods is also welcome: • Non-invasive biomarkers for cancer immunotherapy. • Bulk RNA-seq, scRNA-seq, or Rep-seq methods. • Correlation of tumor immune cells with gut microbiota in tumor immunotherapy. • Impact of Teff and Treg balance in the tumor microenvironment on tumor prognosis. • Inflammatory and immune signatures associated with drug response versus resistance in cancer.
The interplay between tumors and their immunologic microenvironment is complex, difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. The present review discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment.
Topic Editor Dr. Lewis Shi received financial support from Varian Medical System, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Tumor immunology and immunotherapy provides a comprehensive account of cancer immunity and immunotherapy. Examining recent results, current areas of interest and the specific issues that are affecting the research and development of vaccines, this book provides insight into how these problems may be overcome as viewed by leaders in the field.
Topic Editor Prof. Aimin Xu receives financial support from Servier Laboratories. The other Topic Editors declare no competing interests with regards to the Research Topic theme.
The HLA FactsBook presents up-to-date and comprehensive information on the HLA genes in a manner that is accessible to both beginner and expert alike. The focus of the book is on the polymorphic HLA genes (HLA-A, B, C, DP, DQ, and DR) that are typed for in clinical HLA laboratories. Each gene has a dedicated section in which individual entries describe the structure, functions, and population distribution of groups of related allotypes. Fourteen introductory chapters provide a beginner's guide to the basic structure, function, and genetics of the HLA genes, as well as to the nomenclature and methods used for HLA typing. This book will be an invaluable reference for researchers studying the human immune response, for clinicians and laboratory personnel involved in clinical and forensic HLA typing, and for human geneticists, population biologists, and evolutionary biologists interested in HLA genes as markers of human diversity. Introductory chapters provide good general overview of HLA field for novice immunologists and geneticists Up-to-date, complete listing of HLA alleles Invaluable reference resource for immunologists, geneticists, and cell biologists Combines both structural and functional information, which has never been compiled in a single reference book previously Serological specificity of allotypes Identity of material sequenced including ethnic origin Database accession numbers Population distribution Peptide binding specificities T cell epitopes Amino acid sequences of allotypes Key references
This book illustrates the significance and relevance of immunotherapy in modern-day therapeutics. Focusing on the application of immunotherapy in oncology, neurodegenerative and autoimmune diseases, it discusses the drug delivery systems, and pre-clinical and clinical methodologies for immunotherapy-based drugs. It also comprehensively reviews various aspects of immunotherapy, such as regulatory affairs, quality control, safety, and pharmacovigilance. Further, the book discusses the in vitro validation of therapeutic strategies prior to patient application and management of immunotherapy-related side effects and presents case studies demonstrating the design and development (pre-clinical to clinical) of immunotherapy for various diseases. It also describes various design considerations and the scale-up synthesis of immunotherapeutics and screening methods. Lastly, it explores the important aspect of cost-effectiveness and rational immunotherapy strategies.
Part 1: Intratumoral Signatures Associated With Immune Responsiveness