Abstract:
:Monoclonal antibodies targeting the regulatory immune "checkpoint" receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has led to a new class of immune-related adverse events. In many respects, these immune toxicities resemble idiopathic autoimmune diseases, such as inflammatory bowel disease, autoimmune hepatitis, rheumatoid arthritis, and vitiligo. Understanding the pathogenesis of these immune toxicities will have implications not only for care of patients receiving checkpoint blockade but may also provide critical insights into autoimmune disease. The gastrointestinal (GI) mucosa is arguably the most complex barrier in the body, host to a diverse commensal microflora and constantly challenged by ingested foreign proteins both of which must be tolerated. At the same time, the GI mucosa must defend against pathogenic microorganisms while maintaining sufficient permeability to absorb nutrients. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut barrier and GI toxicities, such as colitis and hepatitis are indeed among the most common side effects of CTLA-4 blockade and to a lesser extent blockade of PD-1 and PD-L1. High-dose corticosteroids are typically effective for management of both checkpoint colitis and hepatitis, although a fraction of patients will require additional immune suppression such as infliximab. Prompt recognition and treatment of these toxicities is essential to prevent more serious complications.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Dougan Mdoi
10.3389/fimmu.2017.01547subject
Has Abstractpub_date
2017-11-15 00:00:00pages
1547issn
1664-3224journal_volume
8pub_type
杂志文章,评审abstract::Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different dir...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00973
更新日期:2020-05-19 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2019.00917.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
doi:10.3389/fimmu.2019.01528
更新日期:2019-07-02 00:00:00
abstract::Transcriptional activation and repression of genes that are developmentally regulated or exhibit cell-type specific expression patterns is largely achieved by modifying the chromatin template at a gene locus. Complex formation of stable epigenetic histone marks, loss or gain of DNA methylation, alterations in chromoso...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00112
更新日期:2013-05-16 00:00:00
abstract::Immunotherapy using checkpoint inhibitor targeting PD-1 and PD-L1 revolutionized the treatment of microsatellite instable metastatic colon cancer. Such treatment is now a standard of care for these patients. However, when used as monotherapy checkpoint inhibitors targeting PD-1 and PD-L1 are not effective in metastati...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01816
更新日期:2019-08-06 00:00:00
abstract::Both CD4+ and CD8+ Tregs play a critical role in the control of immune responses and immune tolerance; however, our understanding of CD8+ Tregs is limited while they are particularly promising for therapeutic application. We report here existence of highly suppressive human CD8+CD45RClow/- Tregs expressing Foxp3 and p...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.02014
更新日期:2018-01-31 00:00:00
abstract::Natural killer cells (NK) represent a population of lymphocytes involved in innate immune response. In addition to their role in anti-viral and anti-tumor defense, they also regulate several aspects of the allo-immune response in kidney transplant recipients. Growing evidence suggests a key role of NK cells in the pat...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01454
更新日期:2020-07-23 00:00:00
abstract::Candida is a dominant fungal pathogen in immunocompromised hosts, leading to opportunistic infections. Complement with its multifaceted functions is involved in the immune defense against this yeast, and recently several novel aspects have emerged in this old battle. It is clear that Candida can adopt both roles as a ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01471
更新日期:2020-07-14 00:00:00
abstract::Macrophage plasticity is a process that allows macrophages to switch between two opposing phenotypes based on differential stimuli. Interferon γ (IFNγ)-primed macrophages stimulated with lipopolysaccharide (LPS) [M(IFNγ+LPS)] produce high levels of pro-inflammatory cytokines such as IL-12, TNFα, and IL-6 and low level...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02956
更新日期:2020-01-10 00:00:00
abstract::There is a strong correlation between dysregulation of the gastrointestinal microbiota and development of allergic diseases. The most prevalent therapies for relieving asthma symptoms are associated with serious side effects, and therefore novel approaches are needed. Our objective was to elucidate whether oral admini...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01092
更新日期:2020-06-04 00:00:00
abstract::CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questione...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00480
更新日期:2018-03-12 00:00:00
abstract::Sepsis is life-threatening organ dysfunction due to dysregulated response to infection. Patients with sepsis exhibit wide heterogeneity stemming from genetic, molecular, and clinical factors as well as differences in pathogens, creating challenges for the development of effective treatments. Several gaps in knowledge ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01502
更新日期:2018-06-28 00:00:00
abstract::In this review we discuss how the competition for cytokines between different cells of the immune system can shape the system wide immune response. We focus on interleukin-2 (IL-2) secretion by activated effector T cells (T(eff)) and on the competition for IL-2 consumption between T(eff) and regulatory T cells (T(reg)...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00268
更新日期:2012-09-05 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease including the cardiovascular system. Atherosclerosis is the most common cardiovascular complication of SLE and a significant risk factor for morbidity and mortality. Vascular damage/protection mechanism in SLE patients is out of balance, caused by...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.581385
更新日期:2020-11-11 00:00:00
abstract::Mesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isola...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00297
更新日期:2012-09-26 00:00:00
abstract::Human cytomegalovirus (HCMV) is under constant selective pressure from the immune system in vivo. Study of HCMV genes that have been lost in the absence of, or genetically altered by, such selection can focus research toward findings of in vivo significance. We have been particularly interested in the most pronounced ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02214
更新日期:2018-10-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid progenitor and precursor cells at different stages of differentiation, which play an important role in tumor immunosuppression. Glioma is the most common and deadliest primary malignant tumor of the brain, and ample evidence supports key con...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00737
更新日期:2020-04-24 00:00:00
abstract::Have potential clues to an effective gonorrhea vaccine been lurking in international disease surveillance data for decades? While no clinically effective vaccines against gonorrhea have been developed we present direct and indirect evidence that a vaccine is not only possible, but may already exist. Experience from Cu...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00683
更新日期:2019-04-09 00:00:00
abstract::Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantib...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02200
更新日期:2018-10-05 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00475
更新日期:2015-09-15 00:00:00
abstract::Uncontrolled activation of transforming growth factor (TGF)-β results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-β signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibr...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00068
更新日期:2020-02-07 00:00:00
abstract::Responsiveness of maturing natural killer (NK) cells to chemotactic molecules directly affect their retention and relocation in selected bone marrow (BM) microenvironment during development, as well as their localization at sites of immune response during inflammatory diseases. BM is the main site of NK cell generatio...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00012
更新日期:2013-01-30 00:00:00
abstract::This study develops an original co-infection model in mice using Brucella melitensis, the most frequent cause of human brucellosis, and Trypanosoma brucei, the agent of African trypanosomiasis. Although the immunosuppressive effects of T. brucei in natural hosts and mice models are well established, we observed that t...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00903
更新日期:2017-07-31 00:00:00
abstract::Pemphigus foliaceus (PF) is one of the two main forms of pemphigus and is characterized by circulating IgG to the desmosomal cadherin desmoglein 1 (DSG1) and by subcorneal blistering of the skin. The pathomechanism of blister formation in PF is unknown. Previously we have shown that PF IgG induces aggregation of DSG1,...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02635
更新日期:2019-11-12 00:00:00
abstract::CD8+ T cells represent one of the most versatile immune cells critical for clearing away viral infections. Due to their important role, CD8+ T cell activation and memory formation during viral infection have been the focus of several studies recently. Although CD8+ T cell activation and memory formation have been asso...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01013
更新日期:2020-05-22 00:00:00
abstract::Recombinant proteins are gaining enormous importance these days due to their wide application as biopharmaceutical products and proven safety record. Various recombinant proteins of therapeutic and prophylactic importance have been successfully produced in microbial and higher expression host systems. Since there is n...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01919
更新日期:2018-08-23 00:00:00
abstract::Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopon...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01207
更新日期:2018-06-01 00:00:00
abstract::Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is n...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00332
更新日期:2018-02-27 00:00:00
abstract::Autoantibodies directed against citrullinated epitopes of proteins are highly diagnostic of rheumatoid arthritis (RA), and elevated levels of protein citrullination can be found in the joints of patients with RA. Calcium-dependent peptidyl-arginine deiminases (PAD) are the enzymes responsible for citrullination. PAD2 ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01200
更新日期:2017-09-25 00:00:00
abstract::Cigarette smoke (CS) is the major cause of chronic lung injuries, such as chronic obstructive pulmonary disease (COPD). In patients with severe COPD, tertiary lymphoid follicles containing B lymphocytes and B cell-activating factor (BAFF) overexpression are associated with disease severity. In addition, BAFF promotes ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01622
更新日期:2020-07-29 00:00:00
abstract::Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the d...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01497
更新日期:2019-07-02 00:00:00