Interferon-γ: an overview of signals, mechanisms and functions
TLDR
The current understanding of IFN‐γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophages function during infection are reviewed.Abstract:
Interferon-gamma (IFN-gamma) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-gamma ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-gamma signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-gamma are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-alpha, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.read more
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Interferon-Stimulated Genes: A Complex Web of Host Defenses
TL;DR: This review begins by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production and describes ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the Jak-STAT pathway.
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Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing
Gordon Robertson,Martin Hirst,Matthew N. Bainbridge,Misha Bilenky,Yongjun Zhao,Thomas Zeng,Ghia Euskirchen,Bridget Bernier,Richard Varhol,Allen Delaney,Nina Thiessen,Obi L. Griffith,A He,Marco A. Marra,Michael Snyder,Steven J.M. Jones +15 more
TL;DR: ChIP-seq identified 41,582 and 11,004 putative STAT1-binding regions in stimulated and unstimulated cells, respectively, and found 24 loci known to contain STAT1 interferon-responsive binding sites, including 24 that were enriched in sequences similar to known STAT1 binding motifs.
Journal ArticleDOI
CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
Weimin Wang,Michael D. Green,Jae Eun Choi,Miguel Gijón,Paul D. Kennedy,Jeffrey K. Johnson,Peng Liao,Xueting Lang,Ilona Kryczek,Amanda Sell,Houjun Xia,Jiajia Zhou,Gaopeng Li,Jing Li,Wei Li,Shuang Wei,Linda Vatan,Hongjuan Zhang,Wojciech Szeliga,Wei Gu,Rebecca Liu,Theodore S. Lawrence,Candice Lamb,Yuri Tanno,Marcin Cieslik,Everett Stone,George Georgiou,Timothy A. Chan,Arul M. Chinnaiyan,Arul M. Chinnaiyan,Weiping Zou +30 more
TL;DR: Investigation of human transcriptomes before and during nivolumab therapy revealed that clinical benefits correlate with reduced expression of SLC3A2 and increased IFNγ and CD8 and targeting this pathway in combination with checkpoint blockade is a potential therapeutic approach.
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Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression.
Angel Garcia-Diaz,Daniel Sanghoon Shin,Blanca Homet Moreno,Justin Saco,Helena Escuin-Ordinas,Gabriel Abril Rodriguez,Jesse M. Zaretsky,Lu Sun,Willy Hugo,Xiaoyan Wang,Giulia Parisi,Cristina Puig Saus,Davis Y. Torrejon,Thomas G. Graeber,Begonya Comin-Anduix,Siwen Hu-Lieskovan,Robert Damoiseaux,Roger S. Lo,Antoni Ribas +18 more
TL;DR: Analysis of biopsy specimens from patients with melanoma confirmed interferon signature enrichment and upregulation of gene targets for STAT1/STAT2/STAT3 and IRF1 in anti-PD-1-responding tumors.
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Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future
Lieping Chen,Xue Han +1 more
TL;DR: This Review will focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity.
References
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Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
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Cancer immunoediting: from immunosurveillance to tumor escape.
TL;DR: The historical and experimental basis of cancer immunoediting is summarized and its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction are discussed.
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Nitric oxide and macrophage function
TL;DR: Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.
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How cells respond to interferons
TL;DR: The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interFERons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
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STATs and Gene Regulation
TL;DR: The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.