Cancer Immunotherapies From Efficacy To Resistance Mechanisms
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Cancer Immunotherapies: From Efficacy to Resistance Mechanisms by Morten Hansen,Janin Chandra,Fernando Guimaraes,Nicolas Jacquelot,Yoshinobu Koguchi,Nathalie Labarriere,Ilaria Marigo,Lazar Vujanovic Pdf
Dr. Koguchi receives funding from Tesaro, a GSK company, Bristol-Myers Squibb, and Shimadzu Corporation.. Dr. Vujanovic is a co-inventor of a methodology licensed to INmune Bio, Inc. where a selective inhibitor of soluble TNF can be used to prevent or treat malignancies. Dr. Hansen is the recipient of a private grant from Eurostars Eureka. The other Topic Editors declare no competing interests.
Gastrointestinal Cancer Immunotherapy: from Drug Resistance Mechanisms to Overcoming Strategies by Xiaofang Che,Yibo Fan,Jinyan Wang,Chunlei Zheng,Jia Wei Pdf
Gastrointestinal (GI) cancers, including gastric cancer, colon cancer, liver cancer, esophageal cancer, and pancreatic cancer, seriously threaten the health of human beings worldwide with a high rate of morbidity and mortality. The clinical successes achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have opened a new cancer therapy era and brought new hope to cancer patients. However, the overall response rate (ORR) of ICI monotherapy in the non-selective population is only about 20%, in which some patients subsequently develop immunotherapy resistance. Moreover, the remaining 70-80% of patients displayed primary resistance to ICIs, and a few patients even experienced hyper progression disease (HPD). Although PD-L1 expression, mismatch repair deficient (MMRd), high tumor mutational burden (TMB-H) , high homologous recombination deficiency (HRD), and tumor infiltrated immune cells (TILs) are known as effective biomarkers for immunotherapy, growing studies have reported that ICIs could not improve the OS of all patients with PD-L1 expression higher than 50%, and the ORR of MSI-H patients was only about 60%, whereas some patients with low PD-L1 expression or MSS could still benefit from immunotherapy, indicating the complexity of ICI resistance. Therefore, it is of great importance and significance to explore the prediction biomarkers for primary or acquired immunotherapy resistance and elucidate their underlying molecular mechanisms and develop reversal strategies. Due to the multiple steps of the cancer immune cycle and complex immune microenvironment, any disorders of immune cell infiltration or T cell activation, such as lack of antigens and/or their presentation, lack of response to antigen presentation, and T cell priming, could contribute to ICI resistance. The combination with anti-angiogenesis therapy, radiotherapy, chemotherapy, and other ICIs has improved the efficacy of ICI therapy to some extent in the clinic. Although numerous studies related to ICI resistance were reported in GI cancers, due to the strong spatial/temporal heterogeneity and the complex immune microenvironment in different kinds of GI cancers and different individuals, many questions about ICI resistance and reversal strategies remain unsolved. The aim of this Research Topic is to provide a forum to exhibit the latest research achievement related to the exploration of biomarkers for immunotherapy resistance including HPD and the underlying molecular mechanisms, as well as the development of reversal strategies in GI cancers. We hope this Research Topic will lead to a better understanding of precision cancer immunotherapy and provide useful clues for clinical application to benefit more GI cancer patients with immunotherapy.
Combinational Immunotherapy of Cancer: Novel Targets, Mechanisms, and Strategies by Xuyao Zhang,Xian Zeng,Yubin Li,Dianwen Ju Pdf
Cancer immunotherapy, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy, has revolutionized the paradigm in cancer treatment. However, the clinical outcome of immunotherapy varies considerably among patients and only a minority of patients achieve long-term clinical benefits. This is largely attributed to the fact that existing cancer immunotherapies, which concentrate on several classical targets (CTAL-4, PD-1/PD-L1, etc.) and limited types of immune cell populations (T cells), are insufficient to cope with the complexity of highly heterogeneous tumor microenvironment (TME). This calls for more efforts to not only expand our toolbox for manipulating anticancer immunity but also diversify our combinational strategies. To this end, it is urgent to deeper our understanding of cancer immunotherapy by using both experimental and computational methodologies from multi-scale perspectives: 1) novel targets from either tumor cells or non-tumor cells within TME (e.g., tumor intrinsic resistance drivers, new immune checkpoints, neoantigens), 2) in-depth characterization of more immune cell populations (e.g., macrophages, Tregs, B cells) and their interactions and dynamics within TME, 3) landscape of actionable targets in patient populations for combination design. These efforts will open the avenue of rational design of combinational immunotherapies, allowing researchers and clinicians to design novel targeting therapeutics or to optimally orchestrate combinatory strategies aiming to surmount resistance mechanisms and improve clinical outcomes.
Regulation of Cancer Immune Checkpoints by Jie Xu Pdf
This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.
Cancer Immunology and Immunotherapy by Mansoor M. Amiji,Lara Scheherazade Milane Pdf
Delivery Technologies for Immuno-Oncology: Volume 1: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy examines the challenges of delivering immuno-oncology therapies. Immuno-oncology (IO) is a growing field of medicine at the interface of immunology and cancer biology leading to development of novel therapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) and immune checkpoint blockade antibodies, that are clinically approved approaches for cancer therapy. Although currently approved IO approaches have shown tremendous promise for select types of cancers, broad application of IO strategies could even further improve the clinical success, especially for diseases such as pancreatic cancer, brain tumors where the success of IO so far has been limited. Nanotechnology-based targeted delivery strategies could improve the delivery efficiency of IO agents as well as provide additional avenues for novel therapeutic and vaccination strategies. Additionally, a number of locally-administered immunogenic scaffolds and therapeutic strategies, such as the use of STING agonist, could benefit from rationally designed biomaterials and delivery approaches. Delivery Technologies for Immuno-Oncology: Volume 1: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy creates a comprehensive treaty that engages the scientific and medical community who are involved in the challenges of immunology, cancer biology, and therapeutics with possible solutions from the nanotechnology and drug delivery side. Comprehensive treaty covering all aspects of immuno-oncology (IO) Novel strategies for delivery of IO therapeutics and vaccines Forecasting on the future of nanotechnology and drug delivery for IO
Tumor Immunology and Immunotherapy Resistance by Subree Subramanian,Timothy K Starr,Xianda Zhao Pdf
In recent years, cancer immunotherapy has made remarkable progress, revolutionizing cancer treatment. Our Special Issue "Cancer Immunology" in the journal Cancers showcased cutting-edge research and reviews. Building on that success, this new Special Issue explores recent advancements, technologies, and future prospects in cancer immunology, pre-clinical assessments, and clinical trials. While immune checkpoint inhibitors have been transformative, addressing limited response remains crucial. Strategies to overcome resistance, such as combination therapies and targeted pathways, are discussed in the issue. Chimeric antigen receptor (CAR) T cell therapy is an important area of immunotherapy, with exciting findings for enhancing CAR persistence and efficacy. Conventional treatments and monoclonal antibodies also activate immunological mechanisms, boosting cytotoxic efficacy against specific cancers. Identifying biomarkers associated with treatment response is vital for personalized cancer immunotherapy. Potential biomarkers like immune cell densities and estrogen receptor expression are explored in this Issue. The review articles cover advancements in CAR T cell therapy, tumor metabolic alterations, immune suppressive cells, and the role of bacteria in cancer immunotherapy. This Special Issue is a valuable resource for researchers, clinicians, and industry professionals, guiding future developments towards more effective and personalized cancer immunotherapies.
Successes and Challenges of NK Immunotherapy by Benjamin Bonavida,Anahid Jewett Pdf
Successes and Challenges of NK Immunotherapy: Increasing Anti-tumor Efficacy describes the unique therapeutic applications of NK cells to fight cancers and eliminate the bulk and subset of cancer stem cells responsible for metastasis, relapse and recurrences. The book provides information on the development, engineering, mechanisms of action, response to various preclinical models, and applications in various clinical trials. Sections cover the development of highly engineered cytotoxic NK cells, their mechanisms of action, preclinical and clinical applications, the development and application of CAR-NK cells, and new NK-drug conjugates, also emphasizing that activated NK cells can target and kill highly resistant cancer stem cells. Written by the leading experts on NK immunotherapy worldwide, this is a valuable resource for researchers, clinicians and members of the biomedical field who are interested in understanding novel and efficient therapies to fight cancers. Discusses the unique developmental applications of NK immunotherapy against cancers, which differs greatly from other types of immunotherapies Provides up-to-date and highly relevant information through chapters written by the leading researchers in the field Presents a significant number of schematic diagrams for easy understanding and reproducibility
Immune Checkpoint Inhibitors in Cancer by Fumito Ito,Marc Ernstoff Pdf
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.
Immunotherapy in Resistant Cancer: From the Lab Bench Work to Its Clinical Perspectives by Jorge Morales-Montor,Mariana Segovia-Mendoza Pdf
Immunotherapy in Resistant Cancer: From the Lab Bench Work to Its Clinical Perspectives provides high level knowledge on detailed mechanisms of actions and biological interactions of different immune drugs, with an aim of offering researchers and clinicians cutting-edge therapies to overcome drug resistance. The book explains the latest immunotherapies for different types of cancer, helping users carry out research projects or create alternatives for drug development in the pharmaceutical industry. Topics discussed include the relationship between immunotherapy and macrophages, immune checkpoints in different types of cancer, immune cocktails in solid tumors, and immune-phenotyping. Additionally, the book presents basic and clinical data on immunoresistance and glycosylation. This book is a valuable source for cancer researchers, medical doctors, clinicians and members of the biomedical field who must understand certain mechanisms to fight cancer that is resistant to immunotherapy. Provides basic and clinical evidence based on molecular interactions and clinical studies to address the risks and benefits of cancer immunotherapy Presents the results of new immunotherapy trials, discussing the state-of-the-art in different types of cancer Discusses targeted therapies approved by the FDA, along with therapies with clinical potential used in basic studies
Cancer Immunotherapy Principles and Practice, Second Edition by Lisa H. Butterfield, PhD,Howard L. Kaufman, MD, FACS,Francesco M. Marincola, MD, FACS Pdf
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
Oncoimmunology by Laurence Zitvogel,Guido Kroemer Pdf
In this book, leading experts in cancer immunotherapy join forces to provide a comprehensive guide that sets out the main principles of oncoimmunology and examines the latest advances and their implications for clinical practice, focusing in particular on drugs with FDA/EMA approvals and breakthrough status. The aim is to deliver a landmark educational tool that will serve as the definitive reference for MD and PhD students while also meeting the needs of established researchers and healthcare professionals. Immunotherapy-based approaches are now inducing long-lasting clinical responses across multiple histological types of neoplasia, in previously difficult-to-treat metastatic cancers. The future challenges for oncologists are to understand and exploit the cellular and molecular components of complex immune networks, to optimize combinatorial regimens, to avoid immune-related side effects, and to plan immunomonitoring studies for biomarker discovery. The editors hope that this book will guide future and established health professionals toward the effective application of cancer immunology and immunotherapy and contribute significantly to further progress in the field.
Immunotherapy in Resistant Cancer: From the Lab Bench Work to Its Clinical Perspectives by Jorge Morales Montor,Mariana Segovia Pdf
Immunotherapy in Resistant Cancer: From the Lab Bench Work to Its Clinical Perspectives provides high level knowledge on detailed mechanisms of actions and biological interactions of different immune drugs, with an aim of offering researchers and clinicians cutting-edge therapies to overcome drug resistance. The book explains the latest immunotherapies for different types of cancer, helping users carry out research projects or create alternatives for drug development in the pharmaceutical industry. Topics discussed include the relationship between immunotherapy and macrophages, immune checkpoints in different types of cancer, immune cocktails in solid tumors, and immune-phenotyping. Additionally, the book presents basic and clinical data on immunoresistance and glycosylation. This book is a valuable source for cancer researchers, medical doctors, clinicians and members of the biomedical field who must understand certain mechanisms to fight cancer that is resistant to immunotherapy. Provides basic and clinical evidence based on molecular interactions and clinical studies to address the risks and benefits of cancer immunotherapy Presents the results of new immunotherapy trials, discussing the state-of-the-art in different types of cancer Discusses targeted therapies approved by the FDA, along with therapies with clinical potential used in basic studies
Immunotherapy of Hepatocellular Carcinoma by Tim F. Greten Pdf
In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.
Adaptive Immune Resistance in Cancer Therapy by Lin Qi,Zhigang Liu,Ouyang Chen,Hongzhou Cai Pdf
The adaptive immune resistance (AIR) mechanism refers to the various strategies employed by tumours to adapt and ultimately to overcome immune attack. The AIR mechanism was firstly identified in the selective induction of programmed cell death 1 ligand 1 (PDL1) by interferon gamma of tumors. The inhibition of adaptive immune resistance underlies the responses to PD-1 or PD-L1–blocking antibodies, and may have relevance for the development of other cancer immunotherapy strategies. Therefore, identifying specific AIR mechanisms is of great significance to develop novel drugs and enhance the efficacy of cancer treatment. In this research topic, we aim to generate a collection of articles that discuss the AIR mechanisms, the classification of AIRs, and the current and future cancer therapy strategies based on AIR. Of particular, these articles can focus on exploring the AIR mechanisms in different cancer types and further identify the association between AIR and tumour microenvironment (TME).