Abstract:
:It was recently reported that acute influenza infection of the lung promoted distal melanoma growth in the dermis of mice. Melanoma-specific CD8+ T cells were shunted to the lung in the presence of the infection, where they expressed high levels of inflammation-induced cell-activation blocker PD-1, and became incapable of migrating back to the tumor site. At the same time, co-infection virus-specific CD8+ T cells remained functional while the infection was cleared. It was also unexpectedly found that PD-1 blockade immunotherapy reversed this effect. Here, we proceed to ground the experimental observations in a mechanistic immunobiochemical model that incorporates T cell pathways that control PD-1 expression. A core component of our model is a kinetic motif, which we call a PD-1 Double Incoherent Feed-Forward Loop (DIFFL), and which reflects known interactions between IRF4, Blimp-1, and Bcl-6. The different activity levels of the PD-1 DIFFL components, as a function of the cognate antigen levels and the given inflammation context, manifest themselves in phenotypically distinct outcomes. Collectively, the model allowed us to put forward a few working hypotheses as follows: (i) the melanoma-specific CD8+ T cells re-circulating with the blood flow enter the lung where they express high levels of inflammation-induced cell-activation blocker PD-1 in the presence of infection; (ii) when PD-1 receptors interact with abundant PD-L1, constitutively expressed in the lung, T cells loose motility; (iii) at the same time, virus-specific cells adapt to strong stimulation by their cognate antigen by lowering the transiently-elevated expression of PD-1, remaining functional and mobile in the inflamed lung, while the infection is cleared. The role that T cell receptor (TCR) activation and feedback loops play in the underlying processes are also highlighted and discussed. We hope that the results reported in our study could potentially contribute to the advancement of immunological approaches to cancer treatment and, as well, to a better understanding of a broader complexity of fundamental interactions between pathogens and tumors.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Nikolaev EV,Zloza A,Sontag EDdoi
10.3389/fimmu.2019.00004subject
Has Abstractpub_date
2019-01-28 00:00:00pages
4issn
1664-3224journal_volume
10pub_type
杂志文章abstract::In the last few years, there has been a twist in cancer treatment toward immunotherapy thanks to the impressive results seen in advanced patients from several tumor pathologies. Cutaneous melanoma is a highly mutated and immunogenic tumor that has been a test field for the development of immunotherapy. However, there ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01024
更新日期:2017-08-25 00:00:00
abstract::Neddylation is a type of post-translational protein modifications, in which neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently conjugated to the lysine residues of target substrates. The best characterized principal substrates of neddylation are the cullin-RING ligases (CRLs)...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01432
更新日期:2019-06-25 00:00:00
abstract::CLEC12A has been proposed as a suitable target for delivering antigen to dendritic cells (DCs) to enhance vaccine efficacy both in human and mouse. In this study, we have characterized the porcine homolog of CLEC12A (poCLEC12A). Using new monoclonal antibodies (mAb), raised against its ectodomain, poCLEC12A was found ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00863
更新日期:2020-05-13 00:00:00
abstract::Hyaluronan (HA), the major extracellular matrix component, is often anchored to CD44, a family of structurally/functionally important cell surface receptors. Recent results indicate that UV irradiation (UVR)-induced cutaneous squamous cell carcinomas (SCC) overexpress a variety of CD44 variant isoforms (CD44v), with d...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00224
更新日期:2015-05-13 00:00:00
abstract::Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to auto...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00448
更新日期:2018-03-06 00:00:00
abstract::Exposure to traumatic or infectious insults results in a rapid activation of the complement cascade as major fluid defense system of innate immunity. The complement system acts as a master alarm system during the molecular danger response after trauma and significantly contributes to the clearance of DAMPs and PAMPs. ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00543
更新日期:2019-03-21 00:00:00
abstract::Ruggero Ceppellini, who died at the age of 71 in 1988, was one of the most stimulating and original human geneticists of his generation (1). Ceppellini's outstanding contributions to the genetics of the human blood groups, immunoglobulin allotypes and the HLA system epitomize the study of immunogenetics. By using his ...
journal_title:Frontiers in immunology
pub_type: 传,历史文章,杂志文章
doi:10.3389/fimmu.2019.01280
更新日期:2019-06-05 00:00:00
abstract::The progressive infiltration of immune cells is associated with the progression of melanoma. Specifically, Th17 cells in melanoma microenvironment have both antitumor and protumor effects. It is now necessary to understand the contradictory data associated with how Th17 cells play a role in melanoma. This review will ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00187
更新日期:2019-02-08 00:00:00
abstract:Background:Interleukin-9 (IL9) plays a critical role in immunity and the pathogenesis of endometrial cancer (EC), especially endometrioid EC (EEC). This study aimed to identify the IL9+ immune cell subsets and their pleiotropic functions and establish an optimized prognostic nomogram towards the promotion of personaliz...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.544248
更新日期:2020-11-19 00:00:00
abstract::Influenza A virus (IAV) remains a significant global health issue causing annual epidemics, pandemics, and sporadic human infections with highly pathogenic avian or swine influenza viruses. Current inactivated and live vaccines are the mainstay of the public health response to influenza, although vaccine efficacy is l...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00195
更新日期:2016-05-19 00:00:00
abstract::Recent studies have identified CD49a+Eomes- and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes-/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02126
更新日期:2018-09-25 00:00:00
abstract::Mesenchymal stem cells (MSCs) are known to limit immune responses in vivo by multiple soluble factors. Dickkopf-3 (DKK3), a secreted glycoprotein, has recently been identified as a novel immune modulator. Since DKK3 has been reported to be produced by MSCs, we investigated whether DKK3 contributes to the immune suppre...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00645
更新日期:2015-12-24 00:00:00
abstract::Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study w...
journal_title:Frontiers in immunology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.3389/fimmu.2018.00336
更新日期:2018-03-02 00:00:00
abstract::Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study, the origin and molecular mechan...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01064
更新日期:2017-09-04 00:00:00
abstract::Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, im...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02997
更新日期:2018-12-18 00:00:00
abstract::People are constantly exposed to airborne fungal spores, including Aspergillus fumigatus conidia that can cause life-threatening conditions in immunocompromised patients or acute exacerbations in allergics. However, immunocompetent hosts do not exhibit mycoses or systemic inflammation, due to the sufficient but not ex...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00298
更新日期:2020-02-25 00:00:00
abstract::Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by the presence of focal demyelinated plaques. Sufficient clearance of myelin and cellular debris is one of the requirements for proper tissue repair and remyelination. The mechanisms underlying the clearance o...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00950
更新日期:2019-05-03 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::In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine pr...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00081
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abstract::It was recently proposed that T lymphocytes, which closely interact with APCs, can extract surface molecules from the presenting cells when they dissociate. These observations question the classical view of discrete interactions between phenotypically defined cell populations. In this review, we summarize some reports...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00112
更新日期:2014-03-28 00:00:00
abstract::Background: Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. T...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00557
更新日期:2020-04-15 00:00:00
abstract::The CD83 molecule has been identified to be expressed on numerous activated immune cells, including B and T lymphocytes, monocytes, dendritic cells, microglia, and neutrophils. Both isoforms of CD83, the membrane-bound as well as its soluble form are topic of intensive research investigations. Several studies revealed...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00721
更新日期:2020-04-17 00:00:00
abstract::Autoimmune blistering diseases (AIBDs) of the skin are characterized by autoantibodies against different intra-/extracellular structures within the epidermis and at the basement membrane zone (BMZ). Binding of the antibodies to their target antigen leads to inflammation at the respective binding site and degradation o...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02327
更新日期:2019-10-15 00:00:00
abstract::We recently reported that the treatment with nanoparticles (NPs) loaded with tolerogenic cytokines suppressed the manifestations of lupus-like disease induced by the transfer of donor CD4+ T cells from DBA/2 mice into (C57BL/6 × DBA/2)F1 (BDF1) mice. Although the protective effects were ascribed to the induction of ad...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.583338
更新日期:2020-12-16 00:00:00
abstract::Cerebral malaria is a life-threatening complication of malaria in humans, and the underlying pathogenic mechanisms are widely analyzed in a murine model of experimental cerebral malaria (ECM). Here, we show abrogation of ECM by hemocoel sporozoite-induced infection of a transgenic Plasmodium berghei line that overexpr...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02554
更新日期:2019-11-01 00:00:00
abstract::Diet is a major factor determining gut microbiota composition and perturbances in this complex ecosystem are associated with the inflammatory bowel disease (IBD). Here, we used gnotobiotic approach to analyze, how interaction between diet rich in proteins and gut microbiota influences the sensitivity to intestinal inf...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00919
更新日期:2019-04-26 00:00:00
abstract::Lung cancer is the leading cause of cancer-associated deaths worldwide, with non-small cell-lung cancer (NSCLC) accounting for approximately 80% of cases. Immune escape has been demonstrated to play a key role in the initiation and progression of NSCLC, although the underlying mechanisms are diverse and their puzzling...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00676
更新日期:2020-04-28 00:00:00
abstract::HIV-1 controllers (HIC) are extremely rare patients with the ability to control viral replication, maintain unchanging CD4 T-cell count, and evade disease progression for extensive periods of time, in the absence of antiretroviral therapy. In order to establish the representation of key genetic correlates of atypical ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00746
更新日期:2017-06-27 00:00:00
abstract::Memory CD8+ T cells have long been considered a promising population for adoptive cell therapy (ACT) due to their long-term persistence and robust re-stimulatory response. NIH3T3 is an immortalized mouse embryonic fibroblast cell line. We report that NIH3T3-conditioned medium (CM) can augment effector functions of CTL...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00761
更新日期:2019-04-11 00:00:00
abstract::Lyme disease (Borrelia burgdorferi infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27- memory B cells are elevated in untreated Lyme disease, with higher plasmablast levels associated with more rapid resolution of clinical symptoms. Stro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01634
更新日期:2018-07-18 00:00:00