Community Series In Novel Biomarkers For Predicting Response To Cancer Immunotherapy Volume Ii

This Research Topic is the second volume of the “Community Series in Novel Biomarkers for Predicting Response to Cancer Immunotherapy". Please see Volume I here. Immunotherapy has revolutionized the treatment of malignancies. Targeting of immune checkpoints cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has led to improving survival in a subset of patients. Despite their remarkable success, clinical benefit remains limited to only a subset of patients. A significant limitation behind these current treatment modalities is an irregularity in clinical response, which is especially pronounced among checkpoint inhibition. Currently, relevant predictors of cancer immunotherapy response include microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR), expression of PD-L1, tumor mutation burden (TMB), immune genomic characteristics, and tumor infiltrating lymphocytes (TILs). However, none of them have sufficient evidence to be a stratification factor. Moreover, as the combined strategies for effective cancer immunotherapy had been developed in multiple tumors, such as Immunotherapy combined with chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. Therefore, the development of novel biomarkers endowed with high sensitivity, specificity and accuracy able to identify which patients may truly benefit from the treatment with cancer immunotherapy would allow to refine the therapeutic selection and to better tailor the treatment strategy. This research topic aims to focus on the advances in the discoveries of novel biomarkers for predicting response to cancer immunotherapy in various tumors. We welcome the submission of original research and review articles that include biomarkers in clinical study and applications, as well as technologies or discoveries in experimental approaches.

Immunotherapy has revolutionized the treatment of malignancies. Targeting of immune checkpoints cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has led to improving survival in a subset of patients. Despite their remarkable success, clinical benefit remains limited to only a subset of patients. A significant limitation behind these current treatment modalities is an irregularity in clinical response, which is especially pronounced among checkpoint inhibition. Currently, relevant predictors of cancer immunotherapy response include microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR), expression of PD-L1, tumor mutation burden (TMB), immune genomic characteristics, and tumor infiltrating lymphocytes (TILs). However, none of them have sufficient evidence to be a stratification factor. Moreover, as the combined strategies for effective cancer immunotherapy had been developed in multiple tumors, such as Immunotherapy combined with chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. Therefore, the development of novel biomarkers endowed with high sensitivity, specificity and accuracy able to identify which patients may truly benefit from the treatment with cancer immunotherapy would allow to refine the therapeutic selection and to better tailor the treatment strategy.

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.

This book provides a comprehensive overview of the fast-evolving subject of clinical application of cancer therapeutic biomarkers. The second edition captures significant progress of cancer immunotherapy and emphasizes the genetic basis for selective cancer treatment. It covers an in-depth insight on biomarkers across a broad area of cancer research and oncology with a wealth of integrated genetic and molecular information about specific therapies by a multidisciplinary team of internationally recognized experts. Each chapter focuses on a class of targeted, immunologic, or chemotherapy agents and their companion biomarkers that predict response, benefit or resistance, and severe adverse event. The book will serve as a handbook for health professionals and scientists on the current applicable biomarkers in the management of cancer. The vision into the systemic classification and statistical consideration of therapeutic biomarkers summarized by the book editors and chapter authors will help advance precision medicine—a precisely tailored cancer treatment strategy for cancer patient care.

“Precision/personalized or stratified medicine” refers to the tailoring of medical treatment or drug administration to the individual characteristics of each patient treatment. It does not literally mean that a pharmaceutical company makes a drug for an individual patient for consumption and treatment but rather means the ability to stratify (or classify) individuals into sub-populations that differ in their responsiveness to a specific drug. A marker that provides information on the likely response to therapy, i.e., either in terms of tumor shrinkage or survival of the patient is termed “predictive biomarker”. Despite their promise in precision medicine and the explosion of knowledge in this area, there is not a single source on this subject that puts all this evidence together in a concise or richly illustrated and easy to understand manner. This book provides a collection of ingeniously organized, well-illustrated and up-to-date authoritative chapters divided into five sections that are clear and easy to understand. Section one provides an overview of biomarkers, introduces the basic terminologies, definitions, technologies, tools and concepts associated with this subject in the form of illustrations/graphics, photographs and concise texts. Several recent biomarker endeavors that have been initiated and funded by the National Cancer Institute, National Institutes of Health, FDA and other International organizations are presented. Section two involves the signaling pathways controlling cell growth and differentiation altered in cancer. This section analyzes how predictive biomarkers are altered (expressed or amplified) across cancer types. Section three explores how predictive biomarkers play a role in patient stratification and tailored treatment in relationship to specific cancers. In addition, it includes discussion on the various precision medicine initiatives that are going on across the globe (e.g. TARGET, NCI-MATCH, BATTLE, SHIVA, etc.). Section four discusses: (a) how pharmaceutical companies validate predictive biomarker assays and accompanying companion diagnostics either internally or externally with partner companies such as central laboratories or clinical research organizations, and (b) how predictive biomarker tests fall under the oversight of US FDA, Centers for Medicare & Medicaid Services (CMS) and state laws. Section five wraps up novel agents and targets that are being used as targets for cancer therapeutics. The biomarkers associated with these protocols will also be presented. Throughout the book, sidebars, special interest boxes and illustrations are used to explain terms that are either newly introduced, uncommon, or specialized. Predictive Biomarkers in Oncology will serve as a definitive guide for practicing pathologists, oncologists, basic researchers, and personnel in the pharmaceutical or diagnostic industry interested in learning how “predictive biomarkers” are used in precision cancer therapy.

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.