The Immune Synapse As A Novel Target For Therapy

This volume gives an overview on the progress in immune synapse research, from basic science to clinical trials, and the major mechanisms involved. It discusses how interfering with T cell activation may lead to immune tolerance, immune modulation, and the recruitment of regulatory T cells; the role of monoclonal antibodies in tolerance induction; and mechanisms maintaining dominant tolerance.

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.

Cardiomyopathy is one of the most frequent causes of heart failure. It is often associated with inadequate heart pumping or other heart function abnormalities. There are many different causes of the disease, therefore many different kinds of cardiomyopathies exist. This volume, written by a leading expert, focuses on inflammatory CM, belonging to the Dilated Cardiomyopathies (DCMi). It covers epidemiology/prognosis, pathology, immunology, diagnosis and treatment strategies.

Inflammatory cell recruitment requires the concerted action of at least five major sets of adhesion molecules: integrins, immunoglobulin-like molecules, selectins, carbohydrate structures serving as selectin ligands, and certain ectoenzymes. This volume gives a comprehensive overview on the most relevant leukocyte and endothelial adhesion molecules. The chapters are written by leaders in the field and focus on the biology, structure, function, and regulation of adhesion molecules. Currently approved adhesion molecule-based therapies are reviewed and an outlook for future approaches is also provided. The book is of interest to clinicians and scientists from immunology, physiology, cancer research, rheumatology, allergology, infectious diseases, gastroenterology, pulmonology and cardiology.

Chemokines play an important role in recruiting inflammatory cells into tissues in response to infection and inflammation. They also play an important role in coordinating the movement of T-cells, B-cells and dentritic cells, necessary to generate an immune response (response to injury, allergens, antigens, invading microorganisms). They selectively attract leukocytes to inflammatory foci, inducing both cell migration and activation. They are involved in various diseases, like atherosclerosis, lung and skin inflammation, multiple sclerosis, or HIV. Volume 2 of this two-volume set discusses the pathophysiology of chemokines. It is divided into two parts: a) chemokines in animal disease models, and b) chemokines as drug targets. Together with volume 1, which discusses the immunobiology of chemokines, both volumes give a comprehensive overview of chemokine biology.

The IL-17 cytokines represent a novel family of cytokines, which defines a new effector T cell, the Th17 cell, and extend the Th1-Th2 paradigm. Th17 cells in part co-express at least IL-17A and IL-17F, IL-21 and IL-22. IL-17 A/F are produced by T cells ( and ), iNKT cells, and possibly neutrophils, dendritic cells and Paneth cells. The regulation of IL-17 family member’s expression, and the identification of effector mechanisms are an area of intense current research. Recognized regulators of IL-17A expression include the nuclear receptor ROR t, proinflammatory cyt- ines such as IL-1, IL-6 with TGF- , IL-21, IL-23 IL-25 in the absence of IFN- and IL-4, which are discussed. Recent data suggest that IL-17A may have a dual fu- tion – pro-inflammatory and anti-inflammatory- suggesting that IL-17A may also contribute to terminate inflammation. Further, a reciprocal regulation of Th17 and regulatory T cells including the role of retinoic acid and TGF- is discussed. The discovery that patients with rheumatoid arthritis, allergic disorders, psor- sis and inflammatory bowel disease express IL-17A generated interest in the medical community and instigated a flurry of experimental research on the potential role of Th17 in inflammatory diseases. Experimental studies confirmed that IL-17A is induced and is critical for the development of allergic lung inflammation, arthritis, bacterial sepsis, experimental allergic encephalomyelitis and myocarditis, as well as other inflammatory con- tions including organ transplantation. The role of IL-17F and IL-22 is still poorly defined and is only slowly emerging.

This much-needed text develops current knowledge on the mechanisms of angiogenesis at the molecular and cellular levels as they relate to inflammation, including acute and chronic inflammation, neurogenic initiation, and the role of the multiple cellular components that comprise inflammation. The volume brings together experts in each of these fields to link the molecular and cellular processes in angiogenesis to those of inflammation and disease, culminating in a discourse on areas for future therapies.

This volume provides new advances regarding the involvement of MMPs in various diseases associated with inflammatory processes. Moreover, the recent development of selective and non selective inhibitors of MMPs give new insights in the relationship between activation of inflammatory cells and tissue remodelling and advise new therapeutics possibilities to the treatment of inflammatory disease. The volume has an international authorship and is written by leading experts in the field.