Immune Regulation News Volume 7.02 | Jan 23 2015

Anticancer Immunotherapy by CTLA-4 Blockade: Obligatory Contribution of IL-2 Receptors and Negative Prognostic Impact of Soluble CD25
Investigators show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells, which were otherwise induced by cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade in preclinical mouse models. [Cell Res] Full Article

Commensal Microbiota Influence Systemic Autoimmune Responses
Using mice deficient in lymphotoxin and Hox11, scientists report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. They demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. [EMBO J]
Abstract | Graphical Abstract | Press Release

PD-L1^hi B Cells Are Critical Regulators of Humoral Immunity
Researchers show that regulatory B cells play a critical role in regulating humoral immunity mediated by ​CD4⁺​CXCR5⁺​PD-1⁺ follicular helper T cells, and can suppress inflammation in autoimmune disease through elevated expression of ​PD-L1. [Nat Commun] Abstract

Autophagy Enhances NFκB Activity in Specific Tissue Macrophages by Sequestering ​A20 to Boost Antifungal Immunity
Scientists report a role of autophagy in an early host antifungal response by enhancing NFκB activity through ​A20 sequestration. Enhancement of NFκB activation is achieved by autophagic depletion of ​A20, an NFκB inhibitor, in ​F4/80^hi macrophages in the spleen, peritoneum and kidney. [Nat Commun]
Abstract | Press Release

Cyclic AMP Concentrations in Dendritic Cells Induce and Regulate Th2 Immunity and Allergic Asthma
Scientists show that deletion of Gnas, the gene that encodes Gαs in mouse CD11c⁺ cells, and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. [Proc Natl Acad Sci USA] Abstract | Press Release

Mannose 6 Phosphorylation of Lysosomal Enzymes Controls B Cell Functions
Researchers show that mice deficient in the formation of mannose 6-phosphate residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. [J Cell Biol] Abstract | Press Release | Editorial

Macrophage Peroxisome Proliferator-Activated Receptor γ Deficiency Delays Skin Wound Healing through Impairing Apoptotic Cell Clearance in Mice
Scientists observed that macrophage peroxisome proliferator-activated receptor gamma (PPARγ) expression was upregulated during skin wound healing. Wound macrophages produced higher levels of tumor necrosis factor alpha in PPARγ-knock out mice compared with control. [Cell Death Dis] Full Article

Oncolytic HSV Virotherapy in Murine Sarcomas Differentially Triggers an Antitumor T-Cell Response in the Absence of Virus Permissivity
Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, investigators tested three syngeneic murine sarcoma models that displayed varied degrees of permissiveness to oncolytic herpes simplex virus (HSV) replication and cytotoxicity in vitro, with the most permissive being comparable to some human sarcoma tumor lines. [Mol Ther Oncolytics] Full Article | Press Release

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Controlling the Fire — Tissue-Specific Mechanisms of Effector Regulatory T-Cell Homing
Investigators summarize information on the roles of adhesion molecules and chemokine receptors in mediating regulatory T-cell migration and function throughout the body under homeostatic and inflammatory conditions. [Immunol Cell Biol] Abstract

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Novartis Cosentyx™ Is the First IL-17 Inhibitor to Receive EU Approval for First-Line Treatment of Moderate-to-Severe Psoriasis Patients
Novartis announced that the European Commission has approved Cosentyx™ (secukinumab) as a first-line systemic treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy. [Novartis AG] Press Release

Advaxis Announces FDA Acceptance of Its Investigational New Drug Application to Commence First-in-Human Clinical Trials of ADXS-HER2
Advaxis, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug application to conduct a Phase I clinical study of ADXS-HER2 for the treatment of patients with metastatic HER2 expressing solid tumors. [Advaxis, Inc.] Press Release

ImmunID Announces Rapid Enrolment of Patients in Its PREDICT-ID Melanoma Clinical Trial for Prediction of Response to an Immunotherapy
ImmunID announced the enrolment of the first five patients in its PREDICT-ID Melanoma study to assess the predictive value of immune profiles for response to Ipilimumab^®, an immunomodulatory agent. [ImmunID] Press Release

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