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Trends in Immunology

Faustino Mollinedo
Neutrophils are the first responders to inflammation and infection. Recently, an elevated neutrophil-to-lymphocyte ratio has generally become a prognostic indicator of poor overall survival in cancer. Accordingly, heterogeneous ill-defined neutrophil-like populations have been increasingly recognized as important players in cancer development. In addition, neutrophil granule proteins released upon cell activation have been associated with tumor progression; this differential granule mobilization may allow neutrophils - and possibly associated cancer cells - to leave the bloodstream and enter inflamed/infected tissues...
February 15, 2019: Trends in Immunology
Michelle A Sugimoto, Juliana P Vago, Mauro Perretti, Mauro M Teixeira
The termination of inflammation is governed by endogenous molecules collectively referred to as 'mediators of resolution' of inflammation. There is now strong evidence to suggest that failed resolution may underpin autoimmune and inflammatory diseases and could thus be targeted to decrease inflammation. There are many molecules that have been described as mediators of resolution, and new players are still being continuously discovered. To support the emerging field of 'resolution pharmacology', here we discuss the scientific strategies required to qualify a molecule as a resolution mediator...
February 13, 2019: Trends in Immunology
Graeme J Koelwyn, Kathryn J Moore
Macrophages in the heart have dual roles in injury and repair after myocardial infarction, and understanding the two sides of this coin using traditional 'bulk cell' technologies has been challenging. By combining genetic fate-mapping and single-cell transcriptomics, a new study (Nat. Immunol. 2019;20:29-39) reveals how distinct macrophage populations expand and diverge across the healthy heart and after infarction.
February 8, 2019: Trends in Immunology
Timon Damelang, Stephen J Rogerson, Stephen J Kent, Amy W Chung
IgG3 comprises only a minor fraction of IgG and has remained relatively understudied until recent years. Key physiochemical characteristics of IgG3 include an elongated hinge region, greater molecular flexibility, extensive polymorphisms, and additional glycosylation sites not present on other IgG subclasses. These characteristics make IgG3 a uniquely potent immunoglobulin, with the potential for triggering effector functions including complement activation, antibody (Ab)-mediated phagocytosis, or Ab-mediated cellular cytotoxicity (ADCC)...
February 8, 2019: Trends in Immunology
Jürgen Scheller, Erika Engelowski, Jens M Moll, Doreen M Floss
Cytokines control immune-related events and are critically involved in a plethora of physiological and pathophysiological processes including autoimmunity and cancer development. Accordingly, modulation of natural cytokine signaling by antibodies and small molecules has improved therapeutic regimens. Synthetic biology sets out to optimize immunotherapeutics, with chimeric antigen receptor (CAR) T cell immmunotherapy being the first example to combine synthetic biology with genetic engineering during therapy...
February 6, 2019: Trends in Immunology
Daniel F Zegarra-Ruiz, Gretchen E Diehl
In a recent study, Harrison et al. (Science 2019;363;eaat6280) report that RORγt-expressing skin commensal-specific T cells rapidly respond to tissue wounding by producing type 2 T helper cell (Th2) cytokines in mice. The cells constitutively coexpress GATA-3 and type 2 cytokine mRNAs that are translated after injury. These T cells act as sentinels, linking T cell receptor (TCR) recognition of commensals, tissue damage, and wound repair.
February 1, 2019: Trends in Immunology
Shokrollah Elahi
The main role of red blood cells is oxygen-transportation. However, recent studies have unveiled immunomodulatory functions for their immature counterparts, CD71+ erythroid cells, under different physiological and pathological conditions. Here, I provide a perspective on the recent advances in this field to highlight their importance in health and disease.
February 1, 2019: Trends in Immunology
Renee R Wasko, Valerie Horsley
In a recent study, Zhang et al. (Immunity 2019;50:121-136) report that adipocyte atrophy in aged skin increases susceptibility to bacterial infection. Enhanced TGF-β signaling in aged adipocyte progenitor cells induces a fibrotic cell fate that lacks antimicrobial peptides produced by mature adipocytes, highlighting the importance of stromal cells as innate immune effectors.
January 31, 2019: Trends in Immunology
Jona Walk, Jorn E Stok, Robert W Sauerwein
Recently, a population of non-recirculating, tissue-resident memory CD8+ T cells has been identified; cells that seems to act as key sentinels for invading microorganisms with enhanced effector functions. In malaria, the liver represents the first site for parasite development before a definite infection is established in circulating red blood cells. Here, we discuss the evidence obtained from animal models on several diseases and hypothesize that liver-resident memory CD8+ T cells (hepatic TRM ) play a critical role in providing protective liver-stage immunity against Plasmodium malaria parasites...
January 31, 2019: Trends in Immunology
Friedrich A Kunze, Michael O Hottiger
Innate immune cells express pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). Upon binding, PAMPs/DAMPs can initiate an immune response by activating lymphocytes, amplifying and modulating signaling cascades, and inducing appropriate effector responses. Protein ADP-ribosylation can regulate cell death, the release of DAMPs, as well as inflammatory cytokine expression. Inhibitors of ADP-ribosylation (i...
January 15, 2019: Trends in Immunology
Fernando Souza-Fonseca-Guimaraes, Joseph Cursons, Nicholas D Huntington
Immune 'checkpoint' inhibitors can increase the activity of tumor-resident cytotoxic lymphocytes and have revolutionized cancer treatment. Current therapies block inhibitory pathways in tumor-infiltrating CD8+ T cells and recent studies have shown similar programs in other effector populations such as natural killer (NK) cells. NK cells are critical for immunosurveillance, particularly the control of metastatic cells or hematological cancers. However, how NK cells specifically recognize transformed cells and dominant negative feedback pathways, as well as how tumors escape NK cell control, remains undefined...
January 10, 2019: Trends in Immunology
Adriaan A van Beek, Jan Van den Bossche, Pier G Mastroberardino, Menno P J de Winther, Pieter J M Leenen
Aging is a complex process with an impact on essentially all organs. Declined cellular repair causes increased damage at genomic and proteomic levels upon aging. This can lead to systemic changes in metabolism and pro-inflammatory cytokine production, resulting in low-grade inflammation, or 'inflammaging'. Tissue macrophages, gatekeepers of parenchymal homeostasis and integrity, are prime inflammatory cytokine producers, as well as initiators and regulators of inflammation. In this opinion piece, we summarize intrinsic alterations in macrophage phenotype and function with age...
January 6, 2019: Trends in Immunology
Minkyung Song, Juan R Cubillos-Ruiz
Protective anti-tumor immune responses are mediated by effector molecules that enable successful elimination of malignant cells. As the site where transmembrane and secreted proteins are generated, the endoplasmic reticulum (ER) of immune cells plays a key role in this process. Recent studies have indicated that adverse conditions within tumors perturb ER homeostasis in infiltrating immune cells, which can impede the development of effective anti-cancer immunity. Here, we describe how the tumor microenvironment induces ER stress in immune cells, and discuss the detrimental consequences of persistent ER stress responses in intratumoral immune populations...
January 3, 2019: Trends in Immunology
Luca Antonioli, Corrado Blandizzi, Pál Pacher, Martin Guilliams, György Haskó
Quorum sensing was first described as the communication process bacteria employ to coordinate changes in gene expression and therefore, their collective behavior in response to population density. Emerging new evidence suggests that quorum sensing can also contribute to the regulation of immune cell responses. Quorum sensing might be achieved by the ability of immune cells to perceive the density of their own populations or those of other cells in their environment; responses to alterations in cell density might then be coordinated via changes in gene expression and protein signaling...
January 2, 2019: Trends in Immunology
Taryn M Serman, Michaela U Gack
Aberrant expression of T cell-resident programmed cell death protein-1 (PD-1) is known to promote tumor progression. A recent study (Nature 2018;564:130-135) has now identified the E3 ubiquitin ligase FBXO38 as a crucial regulator of PD-1 protein turnover in T cells, providing a novel mechanism for potential use in cancer immunotherapy.
January 1, 2019: Trends in Immunology
Joannie M Allaire, Shauna M Crowley, Hong T Law, Sun-Young Chang, Hyun-Jeong Ko, Bruce A Vallance
No abstract text is available yet for this article.
January 1, 2019: Trends in Immunology
Maria Cristina Mingari, Gabriella Pietra, Lorenzo Moretta
Antibodies directed towards checkpoint inhibitors have unveiled extraordinary potential in cancer therapy. An article by the Vivier group (Cell 2018;175:1731-1743) shows that blocking the HLA-E-specific NKG2A inhibitory receptor, expressed by NK and inducible in T cells, results in benefits against poor prognosis tumors. Moreover, NKG2A and PD-1/PD-L1 mAb combinations unleash tumor-specific T cell proliferation and memory.
January 1, 2019: Trends in Immunology
Karla D Passalacqua, Mary X O'Riordan
In Nature, Gerlach et al. (Nature 2018;563:705-709) report that methicillin-resistant Staphylococcus aureus camouflages its surface by displaying a 'stealth' wall teichoic acid (WTA) isomer. WTA can act as a cloak to limit exposure of surface antigens to the immune system, but this report indicates that even the cloak can become immunologically silent.
January 1, 2019: Trends in Immunology
David A Hume, Katharine M Irvine, Clare Pridans
The mononuclear phagocyte system (MPS) is defined as a cell lineage in which committed marrow progenitors give rise to blood monocytes and tissue macrophages. Here, we discuss the concept of self-proscribed macrophage territories and homeostatic regulation of tissue macrophage abundance through growth factor availability. Recent studies have questioned the validity of the MPS model and argued that tissue-resident macrophages are a separate lineage seeded during development and maintained by self-renewal. We address this issue; discuss the limitations of inbred mouse models of monocyte-macrophage homeostasis; and summarize the evidence suggesting that during postnatal life, monocytes can replace resident macrophages in all major organs and adopt their tissue-specific gene expression...
December 19, 2018: Trends in Immunology
Adrienne M Rothschilds, K Dane Wittrup
A plethora of new cancer immunotherapies are under clinical development individually and in combination for a wide variety of indications, but optimizing therapeutic outcomes will require precise consideration of timing in treatment schedule design. In this review, we summarize the current understanding of the temporal rhythms of the anticancer immune response. Lessons learned in preclinical and clinical studies begin to define a framework for incorporating duration and sequencing into immunotherapy. We also discuss key challenges and opportunities for translation of temporally programmed treatment schedules to the clinic, including alignment of immunological timescales in preclinical models and humans, and the use of current and emerging biomarkers...
December 10, 2018: Trends in Immunology
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