Abstract:
:Immune checkpoint inhibitors that block the programmed cell death protein 1/PD-L1 pathway have significantly improved the survival of patients with advanced melanoma. Immunotherapies are only effective in 15-40% of melanoma patients and resistance is associated with defects in antigen presentation and interferon signaling pathways. In this study, we examined interferon-γ (IFNγ) responses in a large panel of immune checkpoint inhibitor-naïve melanoma cells with defined genetic drivers; BRAF-mutant (n = 11), NRAS-mutant (n = 10), BRAF/NRAS wild type (n = 10), and GNAQ/GNA11-mutant uveal melanomas (UVMs) (n = 8). Cell surface expression of established IFNγ downstream targets PD-L1, PD-L2, HLA-A, -B, and -C, HLA-DR, and nerve growth factor receptor (NGFR) were analyzed by flow cytometry. Basal cellular expression levels of HLA-A, -B, -C, HLA-DR, NGFR, and PD-L2 predicted the levels of IFNγ-stimulation, whereas PD-L1 induction was independent of basal expression levels. Only 13/39 (33%) of the melanoma cell lines tested responded to IFNγ with potent induction of all targets, indicating that downregulation of IFNγ signaling is common in melanoma. In addition, we identified two well-recognized mechanisms of immunotherapy resistance, the loss of β-2-microglobulin and interferon gamma receptor 1 expression. We also examined the influence of melanoma driver oncogenes on IFNγ signaling and our data suggest that UVM have diminished capacity to respond to IFNγ, with lower induced expression of several targets, consistent with the disappointing response of UVM to immunotherapies. Our results demonstrate that melanoma responses to IFNγ are heterogeneous, frequently downregulated in immune checkpoint inhibitor-naïve melanoma and potentially predictive of response to immunotherapy.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Alavi S,Stewart AJ,Kefford RF,Lim SY,Shklovskaya E,Rizos Hdoi
10.3389/fimmu.2018.01414subject
Has Abstractpub_date
2018-06-21 00:00:00pages
1414issn
1664-3224journal_volume
9pub_type
杂志文章abstract::Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However, the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time acco...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00613
更新日期:2014-12-03 00:00:00
abstract::Antibody deficiency or hypogammaglobulinemia can have primary or secondary etiologies. Primary antibody deficiency (PAD) is the result of intrinsic genetic defects, whereas secondary antibody deficiency may arise as a consequence of underlying conditions or medication use. On a global level, malnutrition, HIV, and mal...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00033
更新日期:2019-02-08 00:00:00
abstract::Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through activation of epidermal...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00746
更新日期:2019-04-05 00:00:00
abstract::A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein....
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01663
更新日期:2020-07-10 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::Hematopoietic cell transplantation (HCT) is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a "window of opportunity" for latent Cytomegalovirus (CMV) by releasing it from immune control wit...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00294
更新日期:2016-08-04 00:00:00
abstract::Adoptive cell transfer therapy is currently one of the most promising approaches for cancer treatment. This therapy has some limitations, however, such as the dispersion of in vivo-administered cells, causing only a small proportion to reach the tumor. Nanotechnological approaches could offer a solution for this drawb...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02073
更新日期:2019-08-30 00:00:00
abstract::In human brucellosis, the liver is frequently affected. Brucella abortus triggers a profibrotic response on hepatic stellate cells (HSCs) characterized by inhibition of MMP-9 with concomitant collagen deposition and TGF-β1 secretion through type 4 secretion system (T4SS). Taking into account that it has been reported ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.03036
更新日期:2020-01-21 00:00:00
abstract::Anti-drug antibodies to coagulation factor VIII (fVIII), often termed inhibitors, present the greatest economical and treatment related obstacle in the management of hemophilia A. Although several genetic and environmental risk factors associated with inhibitor development have been identified, the precise mechanisms ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00150
更新日期:2020-02-07 00:00:00
abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial lining (synovitis). The inflammation in the RA joint is associated with and driven by immune cell infiltration, synovial hyperproliferation, and excessive production of proinflammatory mediators, such as tumor nec...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00571
更新日期:2015-11-19 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::CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells that express an invariant T cell receptor (TCR) α-chain and recognize self and foreign glycolipid antigens. They can rapidly respond to agonist activation and stimulate an extensive array of immune responses. Thymic development and functio...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02653
更新日期:2018-11-14 00:00:00
abstract:Background:The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB). Methods:Using a self-validating case-control design, we tested for an assoc...
journal_title:Frontiers in immunology
pub_type: 临床试验,杂志文章
doi:10.3389/fimmu.2018.00309
更新日期:2018-02-23 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2020.562282.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
doi:10.3389/fimmu.2020.625157
更新日期:2020-12-16 00:00:00
abstract::Natural killer (NK) cells are known for their well characterized ability to control viral infections and eliminate tumor cells. Through their repertoire of activating and inhibitory receptors, NK cells are able to survey different potential target cells for various surface markers, such as MHC-I - which signals to the...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00166
更新日期:2016-05-02 00:00:00
abstract::Bone is a highly dynamic organ that is continuously being remodeled by the reciprocal interactions between bone and immune cells. We have originally established an advanced imaging system for visualizing the in vivo behavior of osteoclasts and their precursors in the bone marrow cavity using two-photon microscopy. Usi...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00596
更新日期:2019-03-26 00:00:00
abstract::Scleroderma (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. We have previously demonstrated that low Fli1 expression in SSc fibroblasts and endothelial cells plays an important role in SSc pathogenesis. Cells of myeloid and lymphoid origin also expres...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00800
更新日期:2020-05-19 00:00:00
abstract::Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antib...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00372
更新日期:2014-08-14 00:00:00
abstract::Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly no...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01124
更新日期:2019-05-22 00:00:00
abstract::Natural killer (NK) cells are lymphocytes of the innate immune system able to kill different targets such as cancer cells and virally infected cells without prior activation making then attractive candidates for cancer immunotherapy. Umbilical cord blood (UCB) has become a source of hematopoietic stem cells for transp...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00329
更新日期:2017-03-23 00:00:00
abstract::Allergies and asthma are a major cause of chronic disease whose prevalence has been on the rise. Allergic disease including seasonal rhinitis, atopic dermatitis, urticaria, anaphylaxis, and asthma, are associated with activation of tissue-resident mast cells and circulating basophils. Although these cells can be activ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00175
更新日期:2019-02-07 00:00:00
abstract::Background: Critically ill patients, especially following trauma or extensive surgery, experience a systemic immune response, consisting of a pro-inflammatory as well as a counterbalancing anti-inflammatory response. Pro-inflammation is necessary for the initiation of homeostatic control and wound healing of the organ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00432
更新日期:2019-03-12 00:00:00
abstract::Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexok...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00639
更新日期:2017-06-19 00:00:00
abstract::Mucosal epithelia encounter both physicochemical and biological stress during their life and have evolved several mechanisms to deal with them, including regulation of immune cell functions. Stressed and damaged cells need to be cleared to control local inflammation and trigger tissue healing. Engagement of the activa...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01583
更新日期:2017-11-20 00:00:00
abstract::Periprosthetic inflammatory osteolysis and subsequent aseptic loosening are commonly observed in total joint arthroplasty. Other than revision surgery, few approved treatments are available for this complication. Wear particle-induced inflammation and macrophage polarization state play critical roles in periprosthetic...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00055
更新日期:2017-01-31 00:00:00
abstract::Pertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedu...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01344
更新日期:2019-07-03 00:00:00
abstract::In recent decades, there has been substantial growth in our understanding of the immune system and its role in tumor growth and overall survival. A central finding has been the cross-talk between tumor cells and the surrounding environment or stroma. This tumor stroma, comprised of various cells, and extracellular mat...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00193
更新日期:2019-02-15 00:00:00
abstract::Background and Objectives: The live non-pathogenic Leishmania tarantolae has recently provided a promising approach as an effective vaccine candidate against experimental leishmaniasis (ILL). Here, we evaluated the immunoprotective potential of the live Iranian Lizard Leishmania mixed with CpG adjuvant against L. majo...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01725
更新日期:2020-10-23 00:00:00
abstract::It is now clear that the outcome of an inflammatory process caused by infections depends on the balance of responses by several components of the immune system. Of particular relevance is the interplay between regulatory T cells (Tregs) and CD4+ T cells that produce IL-17 (Th17 cells) during immunoinflammatory events....
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00341
更新日期:2017-04-03 00:00:00
abstract::Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02539
更新日期:2018-11-14 00:00:00