The roles of different forms of IL-15 in human melanoma progression.

Background: Melanoma is a lethal skin cancer, and the risk of developing it is increased by exposure to ultraviolet (UV) radiation. The production of cytokines such as interleukin-15 (IL-15), induced by the exposure of skin cells to UV rays, could also promote melanoma development. The aim of this study is to investigate the possible role of Interleukin-15/Interleukin-15 Receptor α (IL-15/IL-15Rα) complexes in melanoma development.

MicroRNA analysis of Natural Killer cell-derived exosomes: the microRNA let-7b-5p is enriched in exosomes and participates in their anti-tumor effects against pancreatic cancer cells.

Natural Killer (NK) cells are important components of the immune system in the defense against tumor growth and metastasis. They release exosomes containing proteins and nucleic acids, including microRNAs (miRNAs). NK-derived exosomes play a role in the anti-tumor NK cell function since they are able to recognize and kill cancer cells.

The tumor microenvironment drives NK cell metabolic dysfunction leading to impaired antitumor activity.

NK cells represent key players capable of driving antitumor immune responses. However, the potent immunosuppressive activity of the tumor microenvironment (TME) may impair their effector function. Here, we strengthen the importance of metabolic interactions between NK cells and TME and propose metabolic dysfunction as one of the major mechanisms behind NK failure in cancer treatment.

Different effects of NK cells and NK-derived soluble factors on cell lines derived from primary or metastatic pancreatic cancers.

Natural killer (NK) cells are cytotoxic lymphoid cells that play a key role in defenses against tumors. However, their function may be severely impaired in patients with pancreatic adenocarcinoma (PA). Indeed, PA cells release soluble factors, thereby generating an immunosuppressive environment that dysregulates NK-cell cytolytic function and favors tumor immune evasion.

Myeloid derived suppressor cells in tumor microenvironment: Interaction with innate lymphoid cells.

Human myeloid-derived suppressor cells (MDSC) represent a stage of immature myeloid cells and two main subsets can be identified: monocytic and polymorphonuclear. MDSC contribute to the establishment of an immunosuppressive tumor microenvironment (TME). The presence and the activity of MDSC in patients with different tumors correlate with poor prognosis.

Polymorphonuclear Myeloid-Derived Suppressor Cells Are Abundant in Peripheral Blood of Cancer Patients and Suppress Natural Killer Cell Anti-Tumor Activity.

Tumor microenvironment (TME) includes a wide variety of cell types and soluble factors capable of suppressing immune-responses. While the role of NK cells in TME has been analyzed, limited information is available on the presence and the effect of polymorphonuclear (PMN) myeloid-derived suppressor cells, (MDSC). Among the immunomodulatory cells present in TME, MDSC are potentially efficient in counteracting the anti-tumor activity of several effector cells.

Pediatric Tumors-Mediated Inhibitory Effect on NK Cells: The Case of Neuroblastoma and Wilms' Tumors.

Natural killer (NK) cells play a key role in the control of cancer development, progression and metastatic dissemination. However, tumor cells develop an array of strategies capable of impairing the activation and function of the immune system, including NK cells. In this context, a major event is represented by the establishment of an immunosuppressive tumor microenvironment (TME) composed of stromal cells, myeloid-derived suppressor cells, tumor-associated macrophages, regulatory T cells and cancer cells themselves.

Wilms' Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages.

The immune response plays a crucial defensive role in cancer growth and metastasis and is a promising target in different tumors. The role of the immune system in Wilm's Tumor (WT), a common pediatric renal malignancy, is still to be explored. The characterization of the immune environment in WT could allow the identification of new therapeutic strategies for targeting possible inhibitory mechanisms and/or lowering toxicity of the current treatments.

Interleukin-15 and cancer: some solved and many unsolved questions.

Soluble interleukin (IL)-15 exists under two forms: as monomer (sIL-15) or as heterodimeric complex in association with sIL-15Rα (sIL-15/IL-15Rα). Both forms have been successfully tested in experimental tumor murine models and are currently undergoing investigation in phase I/II clinical trials. Despite more than 20 years research on IL-15, some controversial issues remain to be addressed.

Targeting PKCθ Promotes Satellite Cell Self-Renewal.

Skeletal muscle regeneration following injury depends on the ability of satellite cells (SCs) to proliferate, self-renew, and eventually differentiate. The factors that regulate the process of self-renewal are poorly understood. In this study we examined the role of PKCθ in SC self-renewal and differentiation.

Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury.

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by muscle wasting and chronic inflammation, leading to impaired satellite cells (SCs) function and exhaustion of their regenerative capacity. We previously showed that lack of PKCθ in mice, a mouse model of DMD, reduces muscle wasting and inflammation, and improves muscle regeneration and performance at early stages of the disease. In this study, we show that muscle regeneration is boosted, and fibrosis reduced in θ mice, even at advanced stages of the disease.

Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome.

Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by inflammation of entheses and synovium, leading to joint erosions and new bone formation. It affects 10-30% of patients with psoriasis, and has an estimated prevalence of approximately 1%. PsA is considered to be primarily an autoimmune disease, driven by autoreactive T cells directed against autoantigens present in the skin and in the joints.

MicroRNA Expression Profiling in Behçet's Disease.

Background: Behçet's disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. MicroRNAs (miRNAs) are key regulators of immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in BD is not fully elucidated.

Gene Expression Profiling in Behcet's Disease Indicates an Autoimmune Component in the Pathogenesis of the Disease and Opens New Avenues for Targeted Therapy.

Behçet disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. Disease etiopathogenesis is still unclear. We aim to elucidate some aspects of BD pathogenesis and to identify specific gene signatures in peripheral blood cells (PBCs) of patients with active disease using novel gene expression and network analysis.

MicroRNA Expression Profiling in Psoriatic Arthritis.

Background: Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by bone erosions and new bone formation. MicroRNAs (miRNAs) are key regulators of the immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in PsA is not fully elucidated.

Immune Response to and Gluten Sensitivity.

is a double-stranded RNA virus belonging to the family of . The virus is transmitted by the faecal-oral route and infects intestinal cells causing gastroenteritis. Rotaviruses are the main cause of severe acute diarrhoea in children less than 5 years of age worldwide.

Gene Profiling in Patients with Systemic Sclerosis Reveals the Presence of Oncogenic Gene Signatures.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma.

Targeting early PKCθ-dependent T-cell infiltration of dystrophic muscle reduces disease severity in a mouse model of muscular dystrophy.

Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis.

Targeting PKCθ in skeletal muscle and muscle diseases: good or bad?

Protein kinase Cθ (PKCθ) is a member of the novel calcium-independent PKC family, with a relatively selective tissue distribution. Most studies have focused on its unique role in T-lymphocyte activation and suggest that inhibition of PKCθ could represent a novel therapeutic approach in the treatment of chronic inflammation, autoimmunity and allograft rejection. However, considering that PKCθ is also expressed in other cell types, including skeletal muscle cells, it is important to understand its function in different tissues before proposing it as a molecular target for the treatment of immune-mediated diseases.

PKCθ signaling is required for myoblast fusion by regulating the expression of caveolin-3 and β1D integrin upstream focal adhesion kinase.

Fusion of mononucleated myoblasts to form multinucleated myofibers is an essential phase of skeletal myogenesis, which occurs during muscle development as well as during postnatal life for muscle growth, turnover, and regeneration. Many cell adhesion proteins, including integrins, have been shown to be important for myoblast fusion in vertebrates, and recently focal adhesion kinase (FAK), has been proposed as a key mediator of myoblast fusion. Here we focused on the possible role of PKC, the PKC isoform predominantly expressed in skeletal muscle, in myoblast fusion.