Biomarkers For Immunotherapy Of Cancer

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.

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.

During the past few decades, immunotherapy has become an established pillar of cancer treatment improving the survival of numerous patients with diverse solid and hematologic tumors. The leading causes behind the success are the discovery of immune checkpoint inhibitors (ICIs) and the development of chimeric antigen receptor (CAR) T/M/NK cells. As for ICIs, malignancies take advantage of the inhibitory programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) or cytotoxic T-lymphocyte-associated protein (CTLA-4) pathways to evade the immune system, and disruption of the axis by immune checkpoint inhibitors can achieve durable disease remissions, which has been proved by basic researches and (pre-) clinical studies among lung cancer, melanoma, renal cell cancer, head, and neck squamous cell carcinoma, urothelial cancer, and Hodgkin’s disease. However, the 5-year survival rate of patients treated with ICIs varies with each individual and also relies on tumor specific pathological or molecular subtypes. Besides, the efficacy of ICIs is still limited in terms of drug resistance and fewer potential responders. Thus, there is a big challenge to identify and develop more novel reliable ICIs, as well as sensibilize existing ICIs for patients with drug resistance or even for non-responders.

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.

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.

Genitourinary tumors consist of a large variety of malignancies located in the urinary and the reproductive systems, mainly including prostate cancer, bladder cancer, and renal tumors. Apart from surgeries, various systemic treatments have been used for the whole-course management of genitourinary tumors, including radiation therapy, chemotherapy, and hormonal therapy. However, the characteristics of progression, metastasis, and drug resistance deriving from tumors require and breed novel treatments. Furthermore, exploring biomarkers of genitourinary tumors at the early stage is also beneficial to strengthen the management of patients with tumors. Additionally, the diagnostic and prognostic value of the potential biomarkers for immunotherapy and combined therapy of genitourinary tumors are underexplored. On the basis of precision treatments, the advent of immune-based therapies, including immune checkpoint inhibitors (ICIs, antibodies targeting PD-L1 /PD-1 and CTLA-4 pathways), tumor vaccines, and other therapies, has extended the scope of treatment modalities. FDA has until now approved the clinical application of immune checkpoint inhibitors in a wide range of diseases including some types of genitourinary tumors, whereas not all patients with genitourinary tumors are suitable for immune-based therapies, therefore, the understanding of its underlying mechanism is key to develop effective treatments based on current ICI-based immunotherapy.