Immune Regulation News Volume 10.22 | Jun 15 2018

TOP STORY

Alteration of Tumor Metabolism by CD4⁺ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death

Scientists developed a CD4⁺ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, they showed that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species in tumor cells. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Chromatin Remodeling by the NuRD Complex Regulates Development of Follicular Helper and Regulatory T Cells

Researchers showed that Bcl6-dependent control of follicular T cells is mediated by a complex formed between Bcl6 and the Mi-2β-nucleosome-remodeling deacetylase complex. Formation of this complex reflects the contribution of the intracellular isoform of osteopontin, which acts as a scaffold to stabilize binding between Bcl6 and the NuRD complex that together regulate the genetic program of both follicular helper T cells and follicular regulatory T cells. [Proc Natl Acad Sci USA] Abstract

Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity

The authors reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8⁺ and CD4⁺ effector T cells that eliminate tumors. [Cell Rep] Full Article | Graphical Abstract

Regulation of Thymocyte Trafficking by Tagap, a GAP Domain Protein Linked to Human Autoimmunity

The authors showed in mice that Tagap-mediated signaling by the sema3E/plexin-D1 ligand-receptor complex attenuates thymocytes’ adhesion to the cortex through their β1-containing integrins. By promoting thymocyte detachment within the cortex of the thymus, Tagap-mediated signaling enabled their translocation to the medulla, which is required for continued thymic selection. [Sci Signal] Full Article

Pharmacological Inactivation of the PI3K p110δ Prevents Breast Tumor Progression by Targeting Cancer Cells and Macrophages

Investigators found that although no mutations in the p110δ subunit have been detected thus far in breast cancer, the expression of p110δ becomes gradually elevated during human breast cancer progression from grade I to grade III. Pharmacological inactivation of p110δ in mice abrogated the formation of tumors and the recruitment of macrophages to tumor sites and strongly affected the survival, proliferation and apoptosis of grafted tumor cells. [Cell Death Dis] Full Article

mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3⁺ Regulatory T Cells

Researchers demonstrated that inhibition of mechanistic/mammalian target of rapamycin (mTOR) during T cell activation promoted the generation of long-lived central Tregs with a memory-like phenotype in mice. Metabolically, these central memory Tregs possess enhanced spare respiratory capacity, similar to CD8⁺ memory cells. [J Immunol] Abstract

CK2 Controls Th17 and Regulatory T Cell Differentiation through Inhibition of FoxO1

Through use of a genetic approach to target CK2 kinase activity, investigators provide evidence of a major mechanism by which CK2 regulates the Th17/Treg axis through the inhibition of the transcription factor forkhead box protein O1 (FoxO1). [J Immunol] Abstract

Lymph Node γδ and αβ CD8⁺ T Cells Share Migratory Properties

Scientists characterized migratory behavior of endogenous αβ CD8⁺ and γδ T cells in lymph nodes by long-term tracking following in vivo photoconversion. They identified subsets of γδ T cells with distinct circulation kinetics that closely mirrored migratory subsets of αβ CD8⁺ T cells. [Sci Rep] Full Article

Human Gastric Cancer Mesenchymal Stem Cell-Derived IL15 Contributes to Tumor Cell EMT via Up-Regulation of Tregs Ratio and PD-1 Expression in CD4⁺ T Cell

The effects of IL15 secreted by gastric cancer mesenchymal stem cells on gastric cancer (GC) development were evaluated by detecting the stemness, epithelial-mesenchymal transition (EMT) and migration abilities of GC cell lines. [Stem Cells Dev] Abstract

Galectin-7 Promotes Proliferation and Th1/2 Cells Polarization toward Th1 in Activated CD4⁺ T Cells by Inhibiting the TGFβ/Smad3 Pathway

Galectin-7 (Gal-7) enhanced the proliferation of activated CD4⁺ T cells in a dose- and β-galactoside-dependent manner. Gal-7 treatment did not change the ratio of Th2 cells in activated CD4⁺ T cells, while it increased the ratio of Th1 cells. Gal-7 also induced activated CD4⁺ T cells to produce a higher level of IFN-γ and TNF-α and a lower level of IL-10. [Mol Immunol] Abstract

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TGF-β in T Cell Biology: Implications for Cancer Immunotherapy

The authors review current advances in the understanding of the many roles of transforming growth factor beta (TGF-β) in T cell biology in the context of tumor immunity and discuss the possibility to manipulate TGF-β signaling to improve cancer immunotherapy. [Cancers (Basel)] Full Article

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

CureWorks Collaborative Launches to Accelerate Development of Immunotherapy Treatments for Childhood Cancers, Increase Access to Clinical Trials

Seattle Children’s, with participating members Children’s National Health System, BC Children’s Hospital and Children’s Hospital Los Angeles, has launched CureWorks, an international collaborative of leading academic children’s hospitals determined to accelerate the development of immunotherapy treatments for childhood cancer. CureWorks focuses on expanding immunotherapy trials and patient access around the world, as well as sharing data and collective expertise to advance novel cell therapies. [Seattle Children’s Hospital] Press Release

Arcus Biosciences Announces FDA Clearance of INDs for AB928 and AB122 and Initiation of Phase I/Ib Program to Evaluate AB928 Combinations

Arcus Biosciences, Inc. announced that the FDA has cleared Investigational New Drug (IND) applications for the company’s two most advanced product candidates, AB928 and AB122. Clearance of the first IND for AB928 allows the Company to proceed with its planned Phase I/Ib trial to evaluate the safety, tolerability and preliminary efficacy of AB928 in combination with other agents, including AB122 and chemotherapy, in patients with breast and gynecologic malignancies. [Arcus Biosciences, Inc.] Press Release

OncoMed Doses First Patient in Phase Ib Portion of Anti-TIGIT Clinical Trial

OncoMed Pharmaceuticals Inc. announced that the first patient has been dosed in the company’s Phase Ib portion of the Phase Ia/Ib clinical trial of anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) in combination with anti-PD1. OncoMed’s anti-TIGIT candidate is an IgG1 monoclonal antibody checkpoint inhibitor which binds to the human TIGIT receptor on T-cells with a goal of improving the activation and effectiveness of T-cell and NK cell tumor-killing activity. [OncoMed Pharmaceuticals Inc.] Press Release

New Zealand Appoints First Female Chief Scientific Adviser

The New Zealand government has appointed biochemist Juliet Gerrard as its next chief scientific adviser — the first woman to hold the position. [Nature News] Editorial

Bill to Encourage Generic-Drug Development Passes a Key Hurdle

A key Senate committee voted to advance legislation that aims to spur the development of new generic drugs and in turn, lower drug prices. [Stat News] Editorial

Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study

Sexual harassment is pervasive throughout academic science in the United States, driving talented researchers out of the field and harming others’ careers, finds a report from the US National Academies of Sciences, Engineering, and Medicine in Washington DC. The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial

North American Universities Increasingly Cancel Publisher Packages

Florida State University (FSU) will head into negotiations with the publisher Elsevier to see how it can resolve a pricing issue. Back in April, FSU announced that it would not renew a so-called “big deal” with Elsevier in 2019, due to its “high and ever-increasing cost,” and would instead subscribe to a subset of the most-needed journals. [The Scientist] Editorial

NEW Keystone Symposia: Integrated Pathways of Disease in NASH and NAFLD
January 4-20, 2019
Santa Fe, New Mexico, United States

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NEW PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Human Systems Immunology (University of Oslo)

PhD Position – Characterization of the Immune Pathways that Stimulate Autoimmunity Caused By ADAR1 Deficiency (VIB)

PhD Student Positions – Immunology (Multiple Locations)

Postdoctoral Position – Immunology (Uppsala University)

Postdoctoral Research Scientist – Immunology (Lilly)

Postdoctoral Fellowship – Immunology (University of South Carolina)

Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (Vlaams Instituut voor Biotechnologie)

Postdoctoral Fellow – Immunology (Boston University School of Medicine)

Postdoctoral Fellow – Innate Immune Signaling (Houston Methodist Research Institute)

Postdoctoral Associate Position – Tumor Immunology/Immunotherapy (Duke Cancer Institute)

Assistant, Associate, or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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