Immune Regulation News Volume 9.46 | Dec 1 2017

TOP STORY

Communication between Lung Tumors and Bones Contributes to Tumor Progression

Investigators identified a way in which a type of lung cancer co-opts a portion of the immune system to increase tumor progression. They describe a “crosstalk” between lung tumors and bone marrow, which lead to the generation of a type of immune cell that travels to the tumor and promoted its progression. [Press release from Massachusetts General Hospital discussing online prepublication in Science] Press Release | Abstract

(Ranked by impact factor of the journal)

Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer

Using in vitro-treated non-small-cell lung cancer (NSCLC) cell lines, researchers elucidated an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA induction. Use of this combination treatment schema in mouse models of NSCLC reversed tumor immune evasion and modulated T cell exhaustion state towards memory and effector T cell phenotypes. [Cell] Abstract | Press Release | Graphical Abstract

Myc Cooperates with Ras by Programming Inflammation and Immune Suppression

In a mouse lung model of KRas^G12D-driven adenomas, investigators found that co-activation of Myc drives the immediate transition to highly proliferative and invasive adenocarcinomas marked by highly inflammatory, angiogenic, and immune-suppressed stroma. [Cell] Full Article | Graphical Abstract

The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages

The authors report that the pyroptosis regulator gasdermin D (GSDMD) was necessary for IL-1β secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores were required for IL-1β transport across an intact lipid bilayer. [Immunity] Abstract | Press Release | Graphical Abstract

Remodeling of the Gut Microbiota by Hyperactive NLRP3 Induces Regulatory T Cells to Maintain Homeostasis

Researchers showed that the intestines of cryopyrin-associated periodic syndrome model mice carrying an Nlrp3^R258W mutation maintain homeostasis in the gut. Additionally, such mice were strongly resistant to experimental colitis and colorectal cancer; this was mainly through a remodeled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of Tregs. [Nat Commun] Full Article

Mitochondrial Dynamics Controls Anti-Tumor Innate Immunity by Regulating CHIP-IRF1 Axis Stability

Metabolic shifts in mitochondrial dynamics may be involved in Toll-like receptor agonist-mediated inflammatory responses and immune cell polarization. However, whether the mitochondrial morphology in myeloid immune cells affects anti-tumor immunity is unclear. Scientists showed that FAM73b, a mitochondrial outer membrane protein, has a pivotal function in Toll-like receptor-regulated mitochondrial morphology switching from fusion to fission. [Nat Commun] Full Article

A STAT3-Dependent Transcriptional Circuitry Inhibits Cytotoxic Gene Expression in T Cells

The authors showed that the transcription factors directing IL-17 production, STAT3 and RORγt, inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok, which in CD4⁺ T cells restrains Runx3 functions and cytotoxicity; and STAT3 restrained cytotoxic gene expression in CD8⁺ T cells responding to viral infection in vivo. [Proc Natl Acad Sci USA] Abstract

Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

Investigators showed that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following lymphocytic choriomeningitis virus infection, and this upregulation was dependent on type I interferons. [Cell Rep] Full Article | Graphical Abstract

Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages

Researchers identified a noncanonical pathway for regulation of C-C chemokine ligand 2 (CCL2) production that is mediated by mammalian target of rapamycin complex 1 (mTORC1), but independent of NF-κB. Inhibition of the mTORC1-factor forkhead box K1 (FOXK1) axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. [Cell Rep] Full Article | Graphical Abstract

Hypoxic Lung Cancer-Derived Extracellular Vesicle miR-103a Increases the Oncogenic Effects of Tumor Associated Macrophages by Targeting PTEN

Scientists found that extracellular vesicles (EVs) derived from hypoxic lung cancers increased M2 type polarization by miR-103a transfer. Decreased PTEN levels caused by hypoxic cancer cell-derived EV miR-103a increased activation of AKT and STAT3, and expression of several immunosuppressive and pro-angiogeneic factors. [Mol Ther] Abstract | Full Article | Graphical Abstract

MiR-23b Suppresses Leukocyte Migration and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting CCL7

Investigators found that miR-23b, in addition to its reported functions in suppression of IL-17-associated autoimmune inflammation, halted progression of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, by directly inhibiting migration of pathogenic leukocytes to the central nervous system. [Mol Ther] Abstract

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ZBP1: Innate Sensor Regulating Cell Death and Inflammation

The authors review the history and emergence of Z-DNA-binding protein 1 (ZBP1) as a pathogen sensor and a central regulator of cell death and inflammatory responses. [Trends Immunol] Abstract

Mast Cells as Drivers of Disease and Therapeutic Targets

Scientists discuss the most common approaches for investigating the role and relevance of mast cells in various diseases. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

InDex Pharmaceuticals Reports New Mechanism of Action Data for Cobitolimod

InDex Pharmaceuticals Holding AB announced new scientific data on the mechanism of action of cobitolimod, the company’s lead drug candidate. The findings showed that cobitolimod can modulate the immune system in ulcerative colitis by balancing the mucosal T helper 17/Treg cell response. [InDex Pharmaceuticals Holding AB] Press Release

Cellenkos Inc. Appoints Tara Sadeghi as Senior Director of Clinical Operations

Cellenkos Inc., an early stage clinical biotechnology company developing umbilical cord blood derived Treg cellular therapies for the treatment of autoimmune diseases and inflammatory disorders, announced today that Tara Sadeghi was appointed as Senior Director of Clinical Operations. [Cellenkos Inc. (PR Newswire Association LLC.)] Press Release

Rise in Malaria Cases Sparks Fears of a Resurgence

Progress in the fight against a curable disease that kills hundreds of thousands of children has stalled, according to the World Health Organization. [Nature News] Editorial

Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage

Eager to speed development of revolutionary treatments, the Food and Drug Administration recently announced that it would expedite approval of experimental gene therapies. But the regulatory process may not be the biggest obstacle. [The New York Times] Editorial

China to Roll Back Regulations for Traditional Medicine despite Safety Concerns

Support for traditional medicine in China goes right to the top. President Xi Jinping has called this type of medicine a “gem” of the country’s scientific heritage and promised to give alternative therapies and Western drugs equal government support. Now the country is taking dramatic steps to promote these cures even as researchers raise concerns about such treatments. [Nature News] Editorial

United States Bans Most Government Scientists from Travel to Cuba

The United States’s “new hostile policy towards Cuba undermines confidence” in joint research, says Luis Montero-Cabrera, a chemist at the University of Havana. The Trump administration, adds John Van Horn, a neuroscientist at the University of Southern California in Los Angeles, “has likely shut the door to many U.S.-Cuban interactions.” [ScienceInsider] Editorial

NEW Gordon Research Conferences: Chemotactic Cytokines
June 3-8, 2018
Newry, Maine, United States

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