Abstract:
:Osteocytes are terminally differentiated cells of the osteoblast lineage. They are involved in the regulation of bone remodeling by increasing osteoclast formation or decreasing bone formation by the secretion of the osteoblast inhibitor sclerostin. Monoclonal antibody anti-sclerostin, Romosozumab, has been developed and tested in clinical trials in patients with osteoporosis. In the last years, the role of osteocytes in the development of osteolytic bone lesions that occurs in multiple myeloma, have been underlined. Myeloma cells increase osteocyte death through the up-regulation of both apoptosis and autophagy that, in turn, triggers osteoclast formation, and activity. When compared to healthy controls, myeloma patients with bone disease have higher osteocyte cell death, but the treatment with proteasome inhibitor bortezomib has been shown to maintain osteocyte viability. In preclinical mouse models of multiple myeloma, treatment with blocking anti-sclerostin antibody increased osteoblast numbers and bone formation rate reducing osteolytic bone lesions. Moreover, the combination of anti-sclerostin antibody and the osteoclast inhibitor zoledronic acid increased bone mass and fracture resistance synergistically. However, anti-sclerostin antibody did not affect tumor burden in vivo or the efficacy of anti-myeloma drugs in vitro. Nevertheless, the combination therapy of anti-sclerostin antibody and the proteasome inhibitor carfilzomib, displayed potent anti-myeloma activity as well as positive effects on bone disease in vivo. In conclusion, all these data suggest that osteocytes are involved in myeloma bone disease and may be considered a novel target for the use of antibody-mediated anti-sclerostin therapy also in multiple myeloma patients.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Toscani D,Bolzoni M,Ferretti M,Palumbo C,Giuliani Ndoi
10.3389/fimmu.2018.02467subject
Has Abstractpub_date
2018-10-24 00:00:00pages
2467issn
1664-3224journal_volume
9pub_type
杂志文章,评审abstract::The potential of natural killer (NK) cells to target numerous malignancies in vitro has been well documented; however, only limited success has been seen in the clinic. Although NK cells prove non-toxic and safe regardless of the cell numbers injected, there is often little persistence and expansion observed in a pati...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00264
更新日期:2015-06-03 00:00:00
abstract:Purpose:In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with differ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01903
更新日期:2018-01-08 00:00:00
abstract::Recent clinical observations indicate that bacterial vaccines induce cross-protection against infections produced by different microorganisms. MV130, a polyvalent bacterial sublingual preparation designed to prevent recurrent respiratory infectious diseases, reduces the infection rate in patients with recurrent respir...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.567391
更新日期:2020-11-19 00:00:00
abstract::Viral hemorrhagic fever (VHF) as a disease entity was first codified in the 1930s by soviet scientists investigating patients suffering from hantavirus infection. The group of hemorrhagic fever viruses (HFVs) has since expanded to include members from at least four different virus families: Arenaviridae, Bunyaviridae,...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01202
更新日期:2017-09-26 00:00:00
abstract::Epstein Barr virus (EBV) is a gamma herpes virus associated with certain malignancies and autoimmune diseases. EBV maintains latency in B cells with occasional reactivation, in part by overcoming the host immune response with viral homologs of several human proteins. EBV interleukin 10 (vIL-10), a lytic phase protein,...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02198
更新日期:2018-10-09 00:00:00
abstract::A 65-year-old Italian physician affected by Familial Mediterranean fever (FMF) was hospitalized due to progressive abdominal enlargement, which had begun 6 months before admission. Physical examination revealed ascites and bilateral leg edema. Abdominal CT scan showed ascitic fluid and extensive multiple peritoneal im...
journal_title:Frontiers in immunology
pub_type:
doi:10.3389/fimmu.2020.00889
更新日期:2020-05-13 00:00:00
abstract::Isatuximab is a monoclonal antibody targeting the transmembrane receptor and ectoenzyme CD38, a protein highly expressed on hematological malignant cells, including those in multiple myeloma (MM). Upon binding to CD38-expressing MM cells, isatuximab is thought to induce tumor cell killing via fragment crystallizable (...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01771
更新日期:2020-08-14 00:00:00
abstract::Amino acids (AAs) are necessary nutrients which act not only as building blocks in protein synthesis but also in crucial anabolic cellular signaling pathways. It has been demonstrated that SLC7A5 is a critical transporter that mediates uptake of several essential amino acids in highly proliferative tumors and activate...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00053
更新日期:2018-01-25 00:00:00
abstract::Recognition of cancer antigens drives the clonal expansion of cancer-reactive T cells, which is thought to contribute to restricted T-cell receptor (TCR) repertoires in tumor-infiltrating lymphocytes (TILs). To understand how tumors escape anti-tumor immunity, we investigated tumor-associated T-cell repertoires of pat...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01336
更新日期:2019-06-18 00:00:00
abstract::Background: Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Objective: The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms,...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01654
更新日期:2020-07-31 00:00:00
abstract::Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been recommended as the first-line therapy for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, acquired resistance to EGFR-TKIs is inevitable. Although immune checkpoint blockades (ICBs) targeting the programm...
journal_title:Frontiers in immunology
pub_type:
doi:10.3389/fimmu.2020.01366
更新日期:2020-07-23 00:00:00
abstract::Plasma cells (PCs), the B lineage cells responsible for producing and secreting antibodies (Abs), are critical cellular components of the humoral immune system. While most of the antibody-secreting cells in the body have a rather short lifetime of a few days, some of them can become long-lived and persist in the body ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00788
更新日期:2019-04-24 00:00:00
abstract::The gut epithelium is an ancient site of complex communication between the animal immune system and the microbial world. While elements of self-non-self receptors and effector mechanisms differ greatly among animal phyla, some aspects of recognition, regulation, and response are broadly conserved. A gene regulatory ne...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01297
更新日期:2017-10-23 00:00:00
abstract::Early detection of Primary Immunodeficiencies Disorders (PIDDs) is of paramount importance for effective treatment and disease management. Many PIDDs would be strong candidates for newborn screening (NBS) if robust screening methods could identify patients from dried blood spots (DBS) during the neonatal period. As ma...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00464
更新日期:2020-04-01 00:00:00
abstract::Elimination of potential self-reactive T cells in the thymus is crucial for preventing the onset of autoimmune diseases. Epithelial cell subsets localized in thymic medulla [medullary thymic epithelial cells (mTECs)] contribute to this process by supplying a wide range of self-antigens that are otherwise expressed in ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00249
更新日期:2013-08-26 00:00:00
abstract::Obstructive nephropathy constitutes a major cause of pediatric renal progressive disease. The mechanisms leading to disease progression are still poorly understood. Kidney fibrotic lesions are reproduced using a model of partial unilateral ureteral obstruction (pUUO) in newborn mice. Based on data showing significant ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00450
更新日期:2017-05-04 00:00:00
abstract::Immunotherapies that can either activate or suppress innate immune responses are being investigated as treatments against infectious diseases and the pathology they can cause. The objective of these therapies is to elicit protective immune responses thereby limiting the harm inflicted by the pathogen. The Toll-like re...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00079
更新日期:2014-03-03 00:00:00
abstract::CD4+ regulatory T cells have been intensively studied during aging, but little is still known about age-related changes of other regulatory T cell subsets. It was, therefore, the goal of the present study to analyze CD8+human leukocyte antigen-antigen D related (HLADR)+ T cells in old age, a cell population reported t...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01201
更新日期:2018-06-04 00:00:00
abstract::Systemic Sclerosis (SSc) is a complex auto-immune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin effectively recapitulates the main pathogenic processes and therefore is a good organ to decipher the disease pathophysiology, which remains unclear. However, culturing pr...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.566607
更新日期:2020-10-07 00:00:00
abstract::Despite the role of pigs as a source of new Influenza A Virus viruses (IAV) potentially capable of initiating human pandemics, immune responses to swine influenza virus (SwIV) in pigs are not fully understood. Several SwIV epitopes presented by swine MHC (SLA) class I have been identified using different approaches ei...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02083
更新日期:2020-09-16 00:00:00
abstract::Objectives: Regulatory T cells (Tregs) are frequently functionally impaired in patients with granulomatosis with polyangiitis (GPA). However, the mechanism underlying their impaired function is unknown. Here, we hypothesized that Treg dysfunction in GPA is due to altered microRNA (miRNA) expression. Methods: RNA isola...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02170
更新日期:2019-09-12 00:00:00
abstract::The intestinal mucosa is constantly facing a high load of antigens including bacterial antigens derived from the microbiota and food. Despite this, the immune cells present in the gastrointestinal tract do not initiate a pro-inflammatory immune response. Toll-like receptors (TLRs) are pattern recognition receptors exp...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00060
更新日期:2014-02-18 00:00:00
abstract::Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are activated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically a...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00309
更新日期:2014-07-02 00:00:00
abstract::Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction lead...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00382
更新日期:2016-09-27 00:00:00
abstract::Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunolo...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00732
更新日期:2017-06-26 00:00:00
abstract::COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outco...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.596631
更新日期:2020-12-15 00:00:00
abstract::Because of a loss-of-function mutation in the GGTA1 gene, humans are unable to synthetize α1,3-Galactose (Gal) decorated glycans and develop high levels of circulating anti-α1,3-Galactose antibodies (anti-Gal Abs). Anti-Gal Abs have been identified as a major obstacle of organ xenotransplantation and play a role in se...
journal_title:Frontiers in immunology
pub_type: 杂志文章,meta分析
doi:10.3389/fimmu.2019.03000
更新日期:2020-01-13 00:00:00
abstract::The immunopathological functions associated with human C1q are still growing in terms of novelty, diversity, and pathologic relevance. It is, therefore, not surprising that C1q is being recognized as an important molecular bridge between innate and adaptive immunity. The secret of this functional diversity, in turn, r...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00162
更新日期:2018-02-05 00:00:00
abstract::Impressive clinical efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy for hematological malignancies have prompted significant efforts in achieving similar responses in solid tumors. The lack of truly restricted and uniform expression of tumor-associated antigens, as well as limited T cell persiste...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02268
更新日期:2018-11-19 00:00:00
abstract::Human papillomavirus (HPV) vaccines are safe and effective in preventing HPV infection and cervical precancers. Neutralizing antibodies are thought to be the primary mechanism of protection for HPV vaccines, although the exact level required for protection has not been identified. Three common serological assays used ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.585768
更新日期:2020-10-28 00:00:00