Immune Regulation News Volume 8.44 | Dec 2 2016

TOP STORY

Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity

Previous studies identified the Hippo pathway kinases LATS1/2 as a tumor suppressor, but new research reveals a surprising role for these enzymes in subduing cancer immunity. The findings could have a clinical role in improving efficiency of immunotherapy drugs. [Press release from UC San Diego discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade

Researchers demonstrated that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors. [Cell] Abstract | Graphical Abstract

Trans-Presentation of IL-6 by Dendritic Cells Is Required for the Priming of Pathogenic T_H17 Cells

The authors used a novel strategy for the conditional deletion of distinct interleukin 6 (IL-6)-producing cell types to show that dendritic cells positive for the signaling regulator Sirpα were essential for the generation of pathogenic T_H17 cells. [Nat Immunol] Abstract

Fatty Acid Metabolic Reprogramming via mTOR-Mediated Inductions of PPARγ Directs Early Activation of T Cells

Scientists showed that the mTORC1–PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4⁺ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4⁺ T cells. [Nat Commun] Full Article

Egr2 and Egr3 in Regulatory T Cells Cooperatively Control Systemic Autoimmunity through Ltbp3-Mediated TGF-β3 Production

The authors showed that early growth response gene 2 (Egr2) and Egr3 expressed in T cells cooperatively prevent humoral immune responses by supporting TGF-β3 secretion. T cell-specific Egr2/Egr3 double-deficient mice spontaneously developed an early onset lupus-like disease that was more severe than in T cell-specific Egr2-deficient mice. [Proc Natl Acad Sci USA] Abstract | Full Article

Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8⁺ T Cells

To study the mechanisms controlling tumor rejection, investigators assessed different mouse models for regulatory T-cell (Treg) depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8⁺ T cell-dependent way. [Cancer Res] Abstract

CD4⁺ Virtual Memory: Antigen-Inexperienced T Cells Reside in the Naïve, Regulatory, and Memory T Cell Compartments at Similar Frequencies, Implications for Autoimmunity

Scientists demonstrated that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme, by utilizing the same T cell receptor sequence as their younger counterparts. [J Autoimmun] Full Article | Graphical Abstract

Functional Defects in CD4⁺ CD25^high FoxP3⁺ Regulatory Cells in Ankylosing Spondylitis

Researchers investigated regulatory T cell (Treg) function and found that Tregs in peripheral blood from patients with active ankylosing spondylitis had lower FoxP3 mean fluorescence intensity than those from healthy controls and could not fully suppress naïve T cell proliferation. [Sci Rep] Full Article

Artemisinin Analogue SM934 Attenuate Collagen-Induced Arthritis by Suppressing T Follicular Helper Cells and T Helper 17 Cells

Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4⁺ T cells into Tfh cells and the expression of its transcript factor Bcl-6. [Sci Rep] Full Article

Batf3 Selectively Determines Acquisition of CD8⁺ Dendritic Cell Phenotype and Function

The authors showed that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. [Immunol Cell Biol] Abstract

Circulating CXCR5⁺CD4⁺ T Cells Assist in the Survival and Growth of Primary Diffuse Large B Cell Lymphoma Cells through Interleukin 10 Pathway

Scientists studied the role of the peripheral follicular helper T equivalent, the CXCR5⁺ CD4⁺ T cells, in diffuse large B cell lymphoma (DLBCL). Data showed that compared to CXCR5^– CD4⁺ T cells, CXCR5⁺ CD4⁺ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. [Exp Cell Res] Full Article

Immune Modulation of CD4⁺CD25⁺ Regulatory T Cells by Zoledronic Acid

The authors investigated the immune modulation of regulatory T (Treg) cells by zoledronic acid (ZA). Flow cytometry was used to analyze the phenotypic and immunosuppressive characteristics of Treg cells treated with ZA. [BMC Immunol] Full Article

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Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment

The authors review the current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome. [Int J Mol Sci] Full Article

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

Parker Institute for Cancer Immunotherapy and Cancer Research Institute Launch Collaboration on Cancer Neoantigens

The Parker Institute for Cancer Immunotherapy and the Cancer Research Institute announced a major collaboration focused on neoantigens. The search for these unique cancer markers has become a robust area of research as scientists believe they may hold the key to developing a new generation of personalized, targeted cancer immunotherapies. [Parker Institute for Cancer Immunotherapy] Press Release

ASIT biotech Has Completed the Recruitment of its Phase IIa Clinical Study with hdm-ASIT⁺™ in House Dust Mite Rhinitis

ASIT biotech announced today the recruitment of the last patient in its Phase IIa trial with hdm-ASIT⁺™, its product candidate for house dust mite rhinitis. [ASIT biotech] Press Release

FDA Grants Priority Review to Supplemental Biologics License Application (sBLA) for Merck’s KEYTRUDA^® (Pembrolizumab) in Relapsed or Refractory Classical Hodgkin Lymphoma

Merck announced that the U.S. Food and Drug Administration (FDA) has accepted for review the sBLA for KEYTRUDA^®, the company’s anti-PD-1 therapy, for the treatment of patients with refractory classical Hodgkin lymphoma or for patients who have relapsed after three or more prior lines of therapy. [Merck & Co., Inc.] Press Release

OncoQuest Announces Positive Interim Results from its Phase IIb Clinical Study

OncoQuest Inc. announced positive interim results from the Phase IIb clinical study of its lead product, oregovomab, in patients with advanced epithelial ovarian, adnexal or peritoneal carcinoma. [OncoQuest Inc.] Press Release

Agenus Announces Commencement of Phase I/II Clinical Trial of Anti-OX40 Checkpoint Antibody INCAGN1949 in Patients with Solid Tumors

Agenus Inc. announced that the first patient has been dosed in a Phase I/II clinical trial of the anti-OX40 agonist antibody INCAGN1949. [Agenus Inc.] Press Release

US Health-Reform Legislation Clears Big Hurdle

Legislation that would streamline research and development at the US National Institutes of Health and drug regulation at the Food and Drug Administration is one step closer to becoming law. The US House of Representatives approved the nearly 1,000-page bill — known as the 21^st Century Cures Act — on 30 November. The Senate is expected to take up the controversial US$6.3-billion measure as early as next week. [Nature News] Editorial

Battle over US Overtime Pay Rules Leaves Many Postdocs in Limbo

Institutions struggle to respond after court blocks regulations that would have increased wages for junior researchers. Some universities are proceeding with planned salary increases for postdocs, but others have cancelled — or at least, temporarily halted — changes to researchers’ pay. The uncertainty over how the legal battle will play out is already affecting some postdocs’ career and family plans. [Nature News] Editorial

FDA Chief Pushes Back against Criticism of Stem Cell Treatment Regulations

The country’s top drug regulators pushed back on claims they move too slowly in approving new stem cell treatments and sought to temper expectations for the field’s potential to benefit patients, emphasizing the hazards and the unknowns that persist with developing such therapies. [STAT News] Editorial

Big Biology Projects Warm Up to Preprints

The 4D Nucleome, a major research consortium funded by the US National Institutes of Health, is now requiring that all manuscripts related to its US$120-million, five-year programme are posted to an online preprint server ahead of peer review. And a privately funded, US$600-million biomedical research initiative in California is considering whether to demand its investigators do the same. [Nature News] Editorial

NEW Keystone Symposium: Type I Interferon: Friend and Foe Alike
March 19-23, 2017
Banff, Canada

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NEW Postdoctoral Fellow – Precision Immunology (Icahn School of Medicine at Mount Sinai)

NEW Postdoctoral Research Fellow – Cell Death and Immunity (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Research Fellow – Immune Regeneration (Fred Hutchinson Cancer Research Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham)

Postdoctoral Researcher – Immunology/Molecular Biology (Duke University Department of Medicine)

Postdoctoral Position – Visceral Pain and Neuro-Immune Interaction (KU Leuven)

MRC WIMM Prize PhD Studentships – Various Projects (University of Oxford)

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

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

Postdoctoral Fellow Position – Stem Cell Biology & Immunology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

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