Showing papers in "Trends in Immunology in 2015"

TL;DR: The molecular regulation of T cell exhaustion is reviewed, placing recent findings onPD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell depletion during chronic infection.

TL;DR: Findings from a comprehensive overview of the various sources and multiple reaction partners of NO, and of the regulation of NOS2 by micromilieu factors, antisense RNAs, and 'unexpected' cytokines are discussed.

TL;DR: Evidence indicating that in many settings TAMs fuel, rather than limit, tumor progression, and negatively impact on responses to therapy is discussed, suggesting a molecular understanding of the relationships between TAMs and the tumor microenvironment may lead to improved cancer therapies.

TL;DR: Recent findings demonstrating how the dynamic interactions between neurons and microglia shape the circuitry of the nervous system in the healthy brain and how altered neuron-microglia signaling could contribute to disease are reviewed.

TL;DR: The notion of immune privilege of the CNS is examined in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid to the deep cervical lymph nodes.

TL;DR: How the principles of TCR recognition, including spatial constraints, Kon/Koff rates, and synapse formation, along with in-depth analysis of CAR signaling might be applied to develop safer and more effective synthetic tumor targeting receptors are discussed.

TL;DR: The current knowledge surrounding four main questions are explored: are type I IFN subtypes differentially produced in response to distinct pathogens?

TL;DR: It is proposed that the anti-inflammatory functions of IL-6 may extend to multiple settings and cell types, and it is suggested that these dimensions should be incorporated in therapeutic approaches to these diseases.

TL;DR: It is proposed that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases.

TL;DR: Consider the influence of lipid metabolism and metabolic intermediates on the regulation of signaling and transcriptional pathways via post-translational modifications, and discuss how an improved understanding of FA metabolism may reveal strategies for manipulating immune responses towards therapeutic outcomes.

TL;DR: Data suggest that the extracellular domain of CTLA4 elicits regulatory function, which may lie in regulating localization rather than signaling, and Membrane levels of CT LA4 directly impact access of CD28 to shared ligands.

TL;DR: Findings from recent studies of the functional, biophysical and structural characteristics of IL-2 are reviewed, placing new mechanistic insights into improved next-generation IL- 2 formulations within the broader context ofIL-2 biology and integrating these findings into a framework for understanding IL-1-mediated selective immune modulation.

TL;DR: Recent insights into the role of Tfh cells in disease, how this knowledge may be translated therapeutically, and important areas of further research are discussed.

TL;DR: How the tumor microenvironment modifies metabolic and functional pathways in T cells is reviewed and how these changes may uncover new targets and challenges for cancer immunotherapy and treatment are reviewed.

TL;DR: The interplay between Tregs and metabolism is reviewed, with a particular focus on how host, commensal, and cellular metabolism impinge upon Treg homeostasis and function.

TL;DR: How metabolic pathways might be manipulated for the treatment of human disease is discussed, including how metabolism may be targeted to prevent T cell dysfunction in inhospitable microenvironments, to generate more effective adoptive cellular immunotherapies in cancer, and to direct T cell differentiation and function towards non-pathogenic phenotypes in settings of autoimmunity.

TL;DR: The characteristics of T cell-inflamed versus non-Inflamed tumors, including a type I interferon (IFN) signature associated with T cell priming against tumor antigens, are discussed.

TL;DR: Recent advances in nanoparticle-based approaches aimed at immune-modulation are reviewed in the context of concepts in polymeric nanoparticle development, including particle modification, delivery and the factors associated with successful clinical deployment.

TL;DR: Insights into the cellular and molecular mechanisms underlying neuroinflammation in HD may provide a better understanding of inflammation in more complex neurodegenerative disorders, and of the contribution of the neuroinflammatory component to neurodegenersative disease pathogenesis.

TL;DR: Evidence is reviewed for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways, to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude.

TL;DR: Emerging principles of how this regulation of natural killer cells influences the overall outcome of adaptive immunity in infection and disease are outlined.

TL;DR: The current literature on bioinformatic and statistical analysis of immune repertoire HTS data is reviewed and important directions for future research are highlighted, which could propel immune repertoires HTS to becoming a standard method for measuring adaptive immune responses.

TL;DR: The functional plasticity of IFN signaling is reviewed from a quantitative perspective, showing how variations in different ingredients of the system lead to differential IFN responses and how cells tune the system to maximize efficiency while minimizing detrimental effects.

TL;DR: Current understanding of the roles of mTOR in T cell biology is reviewed, highlighting emerging concepts and areas of investigation where the precise role of m TOR has yet to be fully discerned.

TL;DR: Current models of IgG activity in infectious and inflammatory settings are reviewed, the importance of cell type-specific expression of FcγRs in determining functional outcome is examined, and how this knowledge may be used to improve the activity of therapeutic antibody preparations is discussed.

TL;DR: Recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation are reviewed.

TL;DR: How the CNS immunologically discriminates between pathogens and sterile injuries, mobilizes an immune reaction, and, ultimately, regulates local and peripherally-derived immune cells to provide a supportive milieu for tissue repair is reviewed.

TL;DR: It is proposed that mechanisms associated with ocular immune privilege, in combination with paucity of age-related antigen(s) within the target tissue, dampen what could otherwise be overt inflammation and result in the para-inflammation that characterizes age-associated neurodegenerative disease.

TL;DR: This work discusses environmental signals in early life that are needed for healthy immune homeostasis, and highlights detrimental factors that can set an individual on a path towards disease.

TL;DR: New aspects of myeloid cell biology in general are discussed with special emphasis on the shifting role of microglia during establishment and protection of CNS integrity.