Novel Biomarkers In Tumor Immunity And Immunotherapy

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.

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 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.

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.

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.

Thoroughly updated to reflect major advances in the field of immuno-oncology, this second edition of Cancer Immunotherapy Principles and Practice, from the Society for Immunotherapy of Cancer (SITC), remains the definitive resource for information on tumor immunology and cancer immunotherapy treatments. An essential reference for both novice and experienced cancer researchers, oncologists, and related practitioners alike, the book not only guides readers through the fundamental scientific principles of the field all the way to translational and practical clinical applications for treating and managing oncologic disease, but also provides a comprehensive understanding of the regulatory processes that support the safe and effective delivery of immunotherapy to patients with cancer. The expanded and updated second edition now spans 68 chapters, including 12 new chapters, covering major topics and innovations that have shaped the rapid development of immunotherapy and its ascension into the standard of care as first-line treatment for a growing number of disease settings. New to this edition are chapters with deeper insight into our understanding of cancer genomics and determinants of response, immunogenic cell death, cancer and stromal cell-intrinsic pathways of immune resistance, cancer immune exclusion, adoptive cell therapy, metabolomics, tumor mutation burden, immunotherapy in combination with radiation therapy, synthetic biology, and more. Complete with detailed illustrations, tables, and key points for targeted reference, Cancer Immunotherapy Principles and Practice, Second Edition is the most comprehensive and authoritative resource for scientists and clinicians looking to expand their knowledge base of this dynamic field. Key Features: Offers key insights and perspectives on cancer immunology and immunotherapy treatments from renowned experts in the field Covers the basic principles and science behind cancer immunotherapy and tumor immunology Includes treatment strategies for a vast array of available immunotherapy classes and agents, such as cytokine therapies, oncolytic viruses, cancer vaccines, CAR T therapies, and combination immunotherapies Provides essential information on FDA-approved immunotherapies, including clinical management and outcome data related to response rates, risks, and toxicities Discusses special considerations for immunotherapy in the context of specific disease settings, including skin cancers, genitourinary cancers, gastrointestinal cancers, hepatocellular carcinomas, gynecologic malignancies, breast cancers, lung cancers, head and neck cancers, brain tumors, sarcomas, pediatric cancers, and treatments combined with radiation therapy Clarifies the complex regulatory aspects behind the development and approval of immunotherapy drugs

Precision medicine is an emerging practice by which clinicians aim to deliver a personalized treatment program to affected patients based on information gained from their individual clinical and biological profiles. In the context of precise cancer immunotherapy, multi-omics, high-throughput sequencing, big data, and other approaches serve to screen new predictive factors for immunotherapy response and prognosis in cancer patients.

Bladder cancer is one of the most common urological diseases with a high mortality rate and poor prognosis. It is currently ranked as the 10th most common malignancy worldwide. The majority of bladder cancer patients have been found to be diagnosed with non-muscle invasive bladder cancer (NMIBC) and the remaining, are diagnosed with muscle-invasive bladder cancer (MIBC). Although there have been advances in the treatment and therapies provided for bladder cancer patients, the survival rate remains low, primarily due to recurrence and metastasis of the disease following treatment. Surgical treatment is currently the most common form including radical cystectomy which is the standard form of treatment combined with neoadjuvant chemotherapy. However, the 5-year overall survival rate is 50%. Therefore, further studies are required to understand the molecular mechanisms involved in the progression of bladder cancer and identify novel biomarkers to act as a diagnostic tool for patients. There have been many studies involving the detection of biomarkers in bladder cancer in addition to monitoring disease recurrence to understand the impact and predict potential outcomes. A variety of urine biomarkers have been developed to detect bladder cancer and prognostic risk stratification including mutational DNA and the levels of RNA expression. Circulating tumor cells have also been identified as a potential biomarker for bladder cancer patients. However, there are significant challenges as bladder cancer has demonstrated high levels of cellular and molecular heterogeneity and some markers do not have sufficient sensitivity for accurate detection. Therefore, further studies are required to continue to identify new novel biomarkers for bladder cancer. The aim of this Research Topic is to discuss novel biomarkers in bladder cancer and how it impacts the disease progression and the survival rate for bladder cancer patients.