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Our study further showed the contribution of SEMA3A loss-of-function variants to the pathogenesis of IHH. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.The ability of the immune system to prevent or control the growth of tumor cells is critically dependent on inflammatory processes that lead to the activation, expansion, and recruitment of antitumor effector cells into the tumor microenvironment (TME). These processes are orchestrated by soluble cytokines produced in tissues that alarm local immune surveillance cells (such as dendritic cells, DCs) to mobilize protective antitumor immune populations (B cells, T cells). The interleukin (IL)-36 family of pro-inflammatory cytokines plays an important role in multiple disease processes, ranging from an instigator of autoimmune psoriasis to an initiator of therapeutic immune responses against tumor cells. this website This chapter will focus on the biologic role of immunomodulatory IL-36 family cytokines in the cancer setting and their potential utility in the design of effective interventional therapies. (127 words).Suppression of tumorigenicity 2 (ST2), also known as interleukin-1 receptor-like 1 (IL1RL1), is one of the natural receptors of IL-33. Three major isoforms, ST2L (transmembrane form), sST2 (soluble form), and ST2V, are generated by alternative splicing. Damage to stromal cells induces necrosis and release of IL-33, which binds to heterodimeric ST2L/IL-1RAcP complex on the membrane of a variety of immune cells. This IL-33/ST2L signal induces transcription of the downstream inflammatory and anti-inflammatory genes by activating diverse intracellular kinases and factors to mount an adequate immune response, even in tumor microenvironment. For example, activation of IL-33/ST2L signal may trigger Th2-dependent M2 macrophage polarization to facilitate tumor progression. Notably, sST2 is a soluble form of ST2 that lacks a transmembrane domain but preserves an extracellular domain similar to ST2L, which acts as a "decoy" receptor for IL-33. sST2 has been shown to involve in the inflammatory tumor microenvironment and the progression of colorectal cancer, non-small cell lung cancer, and gastric cancer. Therefore, targeting the IL-33/ST2 axis becomes a promising new immunotherapy for treatment of many cancers. This chapter reviews the recent findings on IL-33/ST2L signaling in tumor microenvironment, the trafficking mode of sST2, and the pharmacological strategies to target IL-33/ST2 axis for cancer treatment.IL-21 is an immunomodulatory cytokine produced by natural killer (NK) cells and T cells that has pleiotropic roles in immune and nonimmune cells. IL-21 can modulate innate and specific immunity activities. It is a potent stimulator of T and natural killer cell-mediated antitumor immunity but also has pro-inflammatory functions in many tissues and is involved in oncogenesis. It is important to understand IL-21 biology in these different situations to ensure the maximal benefit of therapeutic strategies targeting this cytokine. This chapter summarizes IL-21 characteristics and signaling, its role in immune system components, and its use in cancer immunotherapies.Interleukin (IL)-18, a member of the IL-1 family of cytokines, has emerged as a key regulator of mucosal homeostasis within the gastrointestinal tract. Like other members of this family, IL-18 is secreted as an inactive protein and is processed into its active form by caspase-1, although other contributors to precursor processing are emerging.Numerous studies have evaluated the role of IL-18 within the gastrointestinal tract using genetic or complementary pharmacological tools and have revealed multiple roles in tumorigenesis. Most striking among these are the divergent roles for IL-18 in colon and gastric cancers. Here, we review our current understanding of IL-18 biology and how this applies to colorectal and gastric cancers.Inflammation is recognized as representing a double-edged sword in terms of tumor growth, in some instances contributing to attenuation of growth and in others to enhanced progression and metastasis. Extracellular signals, released by cells within the tumor microenvironment (TME), including cancer cells themselves, as well as infiltrating immune cells, stromal cells, and other components of the extracellular matrix, all can contribute to reshaping the tumor microenvironment (TME) and tumor growth/survival. Most recently, attention has centered on contributions in the TME made by the pro-inflammatory interleukin 17 (IL-17) and the T cells (Th17) and non-T cells which produce this cytokine, as well as the target cells (IL-17 receptor positive, IL-17R+) signaled by IL-17. The IL-17 family itself comprises at least six members, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25), and IL-17F, all of which are known to be secreted as disulfide-linked homo- or heterodimers. These in turn bind to IL-17R, a type I cell surface receptor, of which at least five variants have been described to date, IL-17RA to IL-17RE. The discussion below focuses on what we know to date about the role of IL-17/IL-17R interactions in the tumor microenvironment in regulation of tumor growth and metastasis and highlights recent ideas concerning the possible utility of this knowledge in the clinic.T cells can be categorized into functionally diverse subpopulations, which include Th1, Th2, Th9, Th17, Th22, and Tfh cells and Foxp3+ Tregs, based on their role in maintaining normal immune homeostasis and affecting pathological immune-associated diseases. Among these subpopulations, Th9 cells are relatively new, and less is known about their signaling and effects on tumor immunity. Recently, some studies have focused on regulation of the IL-9/IL-9R signaling pathway and Th9 cell differentiation and their roles in tumor environments. Herein, we summarize recent progress in understanding the regulatory signaling of IL-9 and Th9 cells and their critical roles and mechanisms in antitumor immunity.Interleukin (IL)-8 is a chemokine that is essential for inflammation and angiogenesis. IL-8 expression is elevated in tumor cell lines and tissues, as well as in peripheral blood obtained from cancer patients. Primary works have attempted to determine the biological effect of IL-8 on tumor cells, including cell proliferation, survival, and migration. More recently, IL-8 has acquired considerable attention as an immune modulator in the context of certain tumor microenvironments (TME); specifically, it can support a niche that favors tumor progression and metastasis. Tumor-derived IL-8 stimulates inflammation by interacting with the microenvironmental constituents, including fibroblasts, endothelial cells, and immune cells. However, the tumor immune system is complex, and mechanisms that construct the immune phenotype remain incompletely characterized. Herein, we will (1) address a potential role of IL-8 in regulating gene expression to establish immune landscape in tumor. Then, we will (2) review IL-8 signaling in the maintenance of stem cells and regulation of hematopoietic progenitors. Finally, (3) IL-8 functions will be discussed in naturally occurring animal cancers that offer a clinically realistic model for translational research. This chapter will provide a new insight into the tumor immune niche and help us develop immunotherapies for cancers.Interleukin 1 (IL-1) has long been known for its pleiotropic effects on inflammation that plays a complex, and sometimes contrasting, role in different stages of cancer development. As a major proinflammatory cytokine, IL-1β is mainly expressed by innate immune cells. IL-1α, however, is expressed by various cell types under physiological and pathological conditions. IL-1R1 is the main receptor for both ligands and is expressed by various cell types, including innate and adaptive immune cell types, epithelial cells, endothelial cells, adipocytes, chondrocytes, fibroblasts, etc. IL-1 and IL-1R1 receptor interaction leads to a set of common signaling pathways, mainly the NF-kB and MAP kinase pathways, as a result of complex positive and negative regulations. The variety of cell types with IL-1R1 expression dictates the role of IL-1 signaling at different stages of cancer, which under certain circumstances leads to contrasting roles in tumor development. Recent availability of IL-1R1 conditional knockout mouse model has made it possible to dissect the role of IL-1/IL-1R1 signaling transduction in different cell types within the tumor microenvironment. This chapter will focus on the role of IL-1/IL-1R1 in different cell types within the tumor microenvironment and discuss the potential of targeting this pathway in cancer therapy.Since psoriasis is an immuno-mediated skin disease, long-term therapies are necessary for its treatment. In clinical investigations, tacrolimus (TAC), a macrolide immunosuppressive inhibitor of calcineurin, arises as an alternative for the treatment of psoriasis, acting in some cytokines involved in the pathogenesis of the disease. Here, we aim to study the psoriasis treatment with TAC and siRNA for one of most cytokines expressed in psoriasis, the TNF-α. A multifunctional nanostructure lipid carrier (NLC) was developed to co-delivery TAC and siRNA. Results showed that the particle size and zeta potential were around 230 nm and + 10 mV, respectively. The release study demonstrated a controlled release of TAC, and the permeation and retention profile in the skin tissue show to be promising for topical application. The cell viability and uptake in murine fibroblast presented low toxicity associated to uptake of NLC in 4 h, and finally, the in vivo animal model demonstrates the efficiency of the NLC multifunctional, exhibiting a reduction of the cytokine TNF-α expression about 7-fold and presenting a synergic effect between the TAC and TNF-α siRNA. The developed system was successfully to treat in vivo psoriatic animal model induced by imiquimod and the synergic combination was reported here for the first time. Graphical abstract.Lumateperone (Caplyta®) is a novel, orally available agent developed by Intra-Cellular Therapies (under a license from Bristol-Myers Squibb) for the treatment of schizophrenia and other neuropsychiatric and neurological disorders. Lumateperone is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate. In December 2019, lumateperone received its first global approval in the USA for the treatment of schizophrenia in adults. The drug is also under clinical development for bipolar depression, behavioural disorders associated with dementia and Alzheimer's disease, sleep maintenance insomnia and major depressive disorders. This article summarizes the milestones in the development of lumateperone leading to this first approval for the treatment of schizophrenia.Parents frustrated about food marketing influences need media management skills to challenge marketing messages and interpret factual content. We tested a media literacy-based, family-centered intervention to reduce effects of appealing, but unrealistic, food marketing. We hypothesized that participation would facilitate family discussion that improves the home dietary environment and increases youth consumption of fruits and vegetables. Parent-child (age 9-14) dyads (N = 189) participated in a matched-group, pretest/posttest field experiment testing a 6-week media literacy-based curriculum. Hypothesis testing employed multiple analysis of covariance and Bayesian multigroup structural equation modeling (MGSEM). Improved nutrition outcomes for parents included talk with youth about food nutrition labels (d = 0.343) and ratio of healthy to unhealthy food in home (d = 0.232); youth improved talk with parent about food nutrition labels (d = 0.211), vegetables eaten yesterday (d = 0.264), and fruit eaten yesterday (d = 1.