Neuroendocrine Tumors: Germline Genetics and Hereditary Syndromes.

The vast majority of neuroendocrine 'neoplasms (NENs) are sporadic, although recent evidence has indicated that a subset of these cancers may also originate as a result of genetic germline mutations. To date, 10% of these cancers can be linked to an inherited genetic syndrome. Genetic diagnosis is crucial for patients with a suspected hereditary NEN syndrome, as it recognizes patients carrying germline mutations and allows for personalized clinical follow-up, considering the higher risk of developing other tumours.

Two-year follow-up after drug desensitization in mucopolysaccharidosis.

Background: Mucopolysaccharidosis (MPS) type 1 S and type 2 are rare lysosomal storage disorders characterized by impaired enzyme production, resulting in glycosaminoglycans accumulation within lysosomes. Enzyme Replacement Therapy (ERT) with laronidase and idursulfase are first line treatments, respectively. However, infusion-related hypersensitivity reactions (HR) may lead to ERT discontinuation.

The future of cellular therapy for the treatment of renal cell carcinoma.

Introduction: Systemic treatment options for renal cell carcinoma (RCC) have expanded considerably in recent years, and both tyrosine kinase inhibitors and immune checkpoint inhibitors, alone or in combination, have entered the clinical arena. Adoptive cell immunotherapies have recently revolutionized the treatment of cancer and hold the promise to further advance the treatment of RCC.

Areas Covered: In this review, we summarize the latest preclinical and clinical development in the field of adoptive cell immunotherapy for the treatment of RCC, focusing on lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, tumor-infiltrating T cells (TILs), TCR-engineered T cells, chimeric antigen receptor (CAR) T cells, and dendritic cell vaccination strategies.

Cannabidiol modulation of immune cell function: insights and therapeutic implications for atopic dermatitis.

Introduction: Cannabidiol (CBD) exhibits neuroprotective, anti-inflammatory, and immunomodulatory properties, making it a promising candidate for addressing inflammatory skin disorders like atopic dermatitis.

Aim: This study aimed to (i) investigate CBD's impact on lymphocyte proliferation and lymphocyte viability; (ii) assess cytotoxicity U937 cells (a human promonocytic cell line) of CBD/cytotoxicity of CBD on U937 cells; (iii) provide insights into CBD immunomodulatory potential, and (iv) evaluate suitability of CBD for treating inflammatory skin conditions.

Material And Methods: To this aim PBMCs from healthy donors were cultured with mitogen and two different CBD doses (0.

Frequency of sensitization in respiratory allergies: a real-life study with bioinformatic analysis and geographical exploration of allergen prevalence.

Background: and belong to the family (subfamily: "Dermatophagoidinae") and have the respective allergenic proteins of Der p1, Der p2, and Der p23 and Der f1 and Der f2. , belongs to the family (subfamily: "Pyroglyphinae") and its main allergenic protein is Eur m1, a source of sensitization. Sensitization to and is assessed through skin tests, while sensitization to is assessed less frequently.

Angiogenesis in NENs, with a focus on gastroenteropancreatic NENs: from biology to current and future therapeutic implications.

Neuroendocrine neoplasms (NENs) are highly vascularized malignancies arising from cells of the diffuse neuroendocrine system. An intricated cross-talk exists between NEN cells and the tumor microenvironment, and three main molecular circuits (VEGF/VEGFR pathway, FGF-dependent signaling and PDGF/PDGFR axis) have been shown to regulate angiogenesis in these neoplasms. Multiple randomized trials have investigated antiangiogenic agents over the past two decades, and sunitinib is currently approved for the treatment of advanced, progressive, G1/G2 pancreatic NENs.

Role of Wnt-signaling inhibitors DKK-1 and sclerostin in bone fragility associated with Turner syndrome.

Purpose: Girls affected with Turner syndrome (TS) present with low bone mineral density (BMD) and osteopenia/osteoporosis. Thus, they have an increased risk to develop fractures compared to normal population. The aim of this study was to deepen the pathophysiology of skeletal fragility in TS subjects by evaluating the serum levels of Dickkopf-1 (DKK-1) and sclerostin, main regulators of bone mass, as well as the percentage of circulating osteoblast precursors (OCPs).

Direct and Indirect Effect of TGFβ on Treg Transendothelial Recruitment in HCC Tissue Microenvironment.

The balance between anti-tumor and tumor-promoting immune cells, such as CD4+ Th1 and regulatory T cells (Tregs), respectively, is assumed to dictate the progression of hepatocellular carcinoma (HCC). The transforming growth factor beta (TGFβ) markedly shapes the HCC microenvironment, regulating the activation state of multiple leukocyte subsets and driving the differentiation of cancer associated fibroblasts (CAFs). The fibrotic (desmoplastic) reaction in HCC tissue strongly depends on CAFs activity.

Antigen-Specific In Vivo Killing Assay.

The in vivo killing assay allows the quantification of the antigen-specific killing capacity of Cytotoxic CD8 T Lymphocytes (CTLs) in mice. CTLs are indeed known for the lysis of cells expressing foreign or modified antigen peptides on their MHC class I molecules. Here we describe the detailed protocol used for the in vivo specific lysis of cells expressing the H-2 K immunodominant CD8 T-cell epitope of the OVA protein: an 8 amino acid peptide corresponding to the 257-264 region of OVA (SIINFEKL).

Tumor Infiltrating T Cell Cytotoxicity Assay.

Cytotoxicity is the primary function of CD8 T-cells, also called cytotoxic CD8 T lymphocytes (or CTLs). Quantification of this capacity is of major importance in diagnostic and research tools. While phenotypic characterization of CTLs is frequent and easily performed, their function is indeed more difficult to assess.

Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells.

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations.

Safety of measles, mumps, and rubella vaccine in egg allergy: in vivo and in vitro management.

Background: Egg allergy is the second most prevalent form of food allergy in childhood. In spite of the evidence accumulated, inoculating egg allergy children with attenuated vaccines grown on chick embryo cell cultures, such as the measles, mumps, and rubella (MMR) vaccine, is regarded (erroneously) as potentially dangerous or even anaphylactogenic, by many. An issue perceived as particularly conflicting also by Health Professionals.

High levels of gut-homing immunoglobulin A+ B lymphocytes support the pathogenic role of intestinal mucosal hyperresponsiveness in immunoglobulin A nephropathy patients.

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis. The role of the microbiota and mucosal immunity in the pathogenesis of IgAN remains a key element. To date, the hypothetical relationship between commensal bacteria, elevated tumour necrosis factor (TNF) superfamily member 13 [also known as B-cell activating factor (BAFF)] levels, perturbed homoeostasis of intestinal-activated B cells and intestinal IgA class switch has not been clearly shown in IgAN patients.

Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma.

Different subsets of lymphocytes have the capacity to promote or counteract the progression of solid cancers, including hepatocellular carcinoma (HCC). Therefore, to determine the infiltrative ability and functional status of major immune cell subtypes into tumor may lead to novel insights from the perspective of immunotherapy. After obtaining single cell suspensions from freshly collected specimens of HCC tumor, along with paired peritumor tissues and peripheral blood mononuclear cells (PBMCs) from 14 patients, we flow-cytometrically identified and quantified the relative frequencies of lymphocyte subsets within the tissues of origin.

Maintenance-Phase Subcutaneous Immunotherapy with House Dust Mites Induces Cyclic Immunologic Effects.

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment of respiratory allergies including house dust mite (HDM) and Hymenoptera venom allergy. During the build-up phase, the allergen is administered weekly at increasing doses, while during the maintenance phase, it is administered at a fixed high dose every 4 weeks. Upon SCIT injection, the allergen is driven to the draining lymph nodes where it most likely induces an immune response.

Lack of MHC class II molecules favors CD8 T-cell infiltration into tumors associated with an increased control of tumor growth.

Regulatory T-cells (Tregs) are crucial for the maintenance of immune tolerance and homeostasis as well as for preventing autoimmune diseases, but their impact on the survival of cancer patients remains controversial. In the TC-1 mouse model of human papillomavirus (HPV)-related carcinoma, we have previously demonstrated that the therapeutic efficacy of the CyaA-E7-vaccine, targeting the HPV-E7 antigen, progressively declines with tumor growth, in correlation with increased intratumoral recruitment of Tregs. In the present study, we demonstrated that these TC-1 tumor-infiltrating Tregs were highly activated, with increased expression of immunosuppressive molecules.

B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection.

With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs).

Inflammation induces osteoclast differentiation from peripheral mononuclear cells in chronic kidney disease patients: crosstalk between the immune and bone systems.

Background: Inflammation and immune system alterations contribute to bone damage in many pathologies by inducing the differentiation of osteoclasts (OCs), the bone resorbing cells. This link is largely unexplored in chronic kidney disease (CKD) and haemodialysis (HD) patients, in which reduced renal function is accompanied by an increased inflammatory state and skeletal abnormality.

Methods: We used ex vivo culture experiments to investigate the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of CKD and HD patients, focusing on immune cell subsets and inflammatory cytokines such as LIGHT and receptor activator of nuclear factor κB ligand (RANKL).

Plasmacytoid dendritic cells and myeloid cells differently contribute to B-cell-activating factor belonging to the tumor necrosis factor superfamily overexpression during primary HIV infection.

Background: After describing heightened levels of circulating B-cell-activating factor belonging to the tumor necrosis factor superfamily (BAFF) as well as changes in B-cell phenotype and functions during acute infection by simian immunodeficiency virus, we wanted to determine whether and by which cells BAFF was over-expressed in primary HIV-infected (PHI) patients.

Design And Methods: We simultaneously examined circulating BAFF levels by ELISA and membrane-bound BAFF (mBAFF) expression by flow cytometry in peripheral blood mononuclear cells of healthy donors and PHI patients followed for 6 months. We also examined whether HIV-1 modifies BAFF expression or release in various myeloid cells and plasmacytoid dendritic cells (pDC) in vitro.