The complex interactions between the innate and adaptive immune systems function to recognize and clear pathogens or transformed cells, but inefficient interactions between these two systems can result in harmful immunologic responses including chronic infections and the development of cancer. Several hallmarks of dysfunctional adaptive immune responses often detected in tumors share specific features with ineffective immunity in chronic infections. The members of the micromilieu actively participate in the process of tumorigenesis or chronification of infection by modulating innate and adaptive immune system interactions leading e.g. to insufficient T cell responses. The best example is given by the acquisition of an “exhausted” state of cytotoxic CD8+ T cells (CTLs) responding to chronic infections or tumors that are associated with elevated expression of inhibitory receptors and impaired cytokine response. Targeting these major inhibitory pathways by immune checkpoint blockers represents a prime example of successful clinical translation of tumor-specific immunotherapies. Understanding the mechanisms behind (mal)adaptations of the immune system is crucial for achieving therapeutic benefits. The establishment and co-evolution of a dynamic microenvironment niche constituted by the recruitment of numerous cell types dampen immune responses and thus contribute to the development of neoplastic transformation as well as infection. Although there are examples of successful immunotherapeutic approaches (CAR-T cells, immune checkpoint inhibitors, or mRNA vaccination), a large percentage of patients with cancer or chronic infections still do not benefit from these therapies or develop severe immune-related adverse events. The reasons for these failures are not well understood. A possible explanation might be that current immunotherapies target predominantly the effector arm of the immune system by trying to reactivate dysfunctional T cells, but do not sufficiently address the influence of the innate immune system and the contributions of the tumor microenvironment (TME) niche. The main problem we would like to address in this special issue is how inappropriate function of the innate immune system affects adaptive immunity and contributes to inefficient anti-cancer immunity and chronification of infections. The central goal is to provide a more precise understanding of the various (common and novel) immune evasion mechanisms in cancers and in chronic infections to obtain a detailed map of common and disease-specific immune escape checkpoints. To that aim, we want to compile a wide array of interdisciplinary studies exploring a comparative and multi-layered analysis of mechanisms responsible for inefficient immune responses, including novel approaches i.e. multi-omics or epigenetic signaling. We would also like to combine studies from different fields, including basic and clinical immunology, oncology, and virology/microbiology. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case report, and Perspective articles that cover, but are not limited to the following topics: • Convergent mechanisms supporting immune escape in preclinical models (tumors and chronic infections) • Convergent evasion mechanisms mediated by tumor-infiltrating suppressive cells (Treg, MDSC, macro-phages, soluble mediators, signaling, metabolism, ...) • Convergent immune evasion mechanisms mediated by chronic infection (viral or parasite) • Novel strategies to modulate the TME by direct or indirect targeting of immune suppressor cells. • Approaches to enhance persistence and resilience of anticancer T cells • Combinatorial therapeutic strategies (mRNA, antibodies, immune checkpoint blockers …) that target convergent immune evasion mechanisms 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.

One of the ways tumor cells can evade immune detection is by recruiting another immune cell type called macrophages, which are able to suppress anti-tumor CTL activity and promote tumor growth. We developed a model system in which normal immune cells are incubated with lymphoma cells to initiate an immune reaction. When this occurs, factors are secreted into the surroundings that promote the differentiation of cells into immunosuppressive macrophages. Silvestrol, even at extremely low concentrations, blocks both the secretion of the macrophage-inducing factors and also directly inhibits the outgrowth of macrophages even in the presence of suppressive factors. This finding indicates that protein synthesis is important to this immune evasion strategy, and provides a new approach to modulate the immune response in EBV-driven lymphoma and possibly other cancers. In summary, this work provides a strong rationale for continued development of this novel immunotherapeutic approach to treating this aggressive and clinically difficult type of cancer.

This book provides a comprehensive overview of current immunotherapy strategies, and how these may be applicable to childhood cancers. The first part of the book reviews how the immune system recognizes cancer, and the various escape mechanisms allowing tumour growth. The importance of the tumor microenvironment and the challenges this may present to achieving effective immunotherapy are discussed. Monoclonal antibodies, cellular, cytokine and vaccine therapies are all comprehensively reviewed, with particular focus on their potential application to pediatric cancers. Practical aspects of delivering such therapies to children, likely toxicities and potential biomarkers are considered. Finally, consideration is given to how, in the longer term, such therapies may be combined with conventional therapies such as chemotherapy and radiotherapy. Edited by two distinguished pediatric oncologists with a collection of chapters from the most authoritative experts in cancer immunotherapy, this is an indispensable volume for pediatric oncologists and physicians working in childhood cancer care.

This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. 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. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.

This first open access European CAR-T Handbook, co-promoted by the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA), covers several aspects of CAR-T cell treatments, including the underlying biology, indications, management of side-effects, access and manufacturing issues. This book, written by leading experts in the field to enhance readers’ knowledge and practice skills, provides an unparalleled overview of the CAR-T cell technology and its application in clinical care, to enhance readers’ knowledge and practice skills.