Immune Regulation News Volume 7.36 | Sep 25 2015

K33-Linked Polyubiquitination of Zap70 by Nrdp1 Controls CD8⁺ T Cell Activation
Scientists found that Nrdp1, a ring finger–type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase–like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8⁺ T cells. [Nat Immunol] Abstract

Role of T-Cell Reconstitution in HIV-1 Antiretroviral Therapy-Induced Bone Loss
Researchers transplanted T cells into immunocompromised mice to mimic antiretroviral therapy-induced T-cell expansion. T-cell reconstitution elicits receptor activator of NF-κB ligand and TNFα production by B cells and/or T cells, accompanied by enhanced bone resorption and bone mineral density loss. [Nat Commun] Abstract

Cognate Interaction with iNKT Cells Expands IL-10–Producing B Regulatory Cells
Investigators showed that invariant natural killer T (iNKT) cognate help for B cells is fundamentally different from the help provided by conventional CD4⁺ T cells. Cognate iNKT-cell help drives an early, unsustained germinal center B-cell expansion, less reduction of T follicular regulatory cells, an expansion of marginal zone B cells, and early increases in regulatory IL-10–producing B-cell numbers compared with noncognate activation. [Proc Natl Acad Sci USA] Abstract | Full Article

The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance
The authors showed that genetic ablation of nuclear receptor subfamily 2, group F, member 6 (Nr2f6) significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, Nr2f6^−/− mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor rechallenge. [Cell Rep] Full Article | Graphical Abstract

MALT1 Is an Intrinsic Regulator of Regulatory T Cells
Researchers showed that the nuclear factor-κB signaling mediator mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important novel regulator of both Tregs originating in the thymus and Tregs induced to differentiate from naive thymocyte helper cells in the periphery. [Cell Death Differ] Full Article

Lethal Giant Larvae-1 Deficiency Enhances the CD8⁺ Effector T-Cell Response to Antigen Challenge In Vivo
To assess the role of Lgl-1 in T cells, scientists generated chimeric mice with a hematopoietic system deficient for lethal giant larvae-1 (Lgl-1). Lgl-1 deficiency did not impair the activation or function of peripheral CD8⁺ T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. [Immunol Cell Biol] Abstract

RhoB Regulates the Function of Macrophages in the Hypoxia-Induced Inflammatory Response
Researchers investigated the effect of hypoxia on the expression of RhoB and the mechanism and significance of RhoB expression in macrophages. They found that hypoxia significantly upregulated the expression of RhoB in RAW264.7 cells, mouse peritoneal macrophages, and the spleen of rats. [Cell Mol Immunol] Abstract

NOD2 and TLR2 Ligands Trigger the Activation of Basophils and Eosinophils by Interacting with Dermal Fibroblasts in Atopic Dermatitis-Like Skin Inflammation
Scientists used a typical mouse model of atopic dermatitis (AD)-like skin inflammation and found that Staphylococcus aureus-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll-like receptor 2 (TLR2) ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. [Cell Mol Immunol] Abstract

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ZIOPHARM Announces Presentation of Clinical and Preclinical Data from Ad-RTS-IL-12
ZIOPHARM Oncology, Inc. announced the presentation of clinical and preclinical data from the Company’s Ad-RTS-IL-12 program in various malignancies. Ad-RTS-IL-12 is a novel gene therapy candidate for the controlled expression of IL-12, a critical protein for stimulating an anti-cancer T cell immune response. [Press release from ZIOPHARM Oncology, Inc. discussing research presented at the 2015 CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference, New York] Press Release

Cellular Biomedicine Group to Present CAR-T Phase I Clinical Trial Data for Non Small Cell Lung Cancer and Other Solid Tumors
Cellular Biomedicine Group Inc. announced that it would give an oral presentation to discuss Phase I clinical trial data for EGFR (HER-1)-targeted chimeric antigen receptor-modified T-cells (CAR-T) immunotherapy for patients with non-small cell lung cancer and other solid tumors. [Press release from Cellular Biomedicine Group Inc. discussing research to be presented at the 5^th World Congress on Cancer Therapy, Atlanta] Press Release

Celimmune to Present Overview of Non-Dietary Celiac Disease Therapies in Development
Dr. Francisco Leon, CEO and Chief Medical Officer, discussed the characteristics and mechanism of action of several investigational non-dietary treatments for celiac disease and gluten-related conditions, including AMG 714, a Phase II-stage, anti-IL-15 monoclonal antibody that Celimmune is developing for the treatment of diet non-responsive celiac disease and refractory celiac disease type II. [Press release from Celimmune LLC (PR Newswire Association LLC) discussing research to be presented at the Kansas City Gluten & Allergen-Free Wellness Event, Overland Park] Press Release

Enumeral Announces Identification of Anti-PD-1 Antibodies with Potential for Differentiated Mechanism of Action
Enumeral Biomedical Holdings, Inc. announced important progress in its anti-PD-1 antibody program. Enumeral also provided an update on the progress of additional programs in the Company’s R&D pipeline, including its TIM-3 and LAG-3 antibody programs. [Press release from Enumeral Biomedical Holdings, Inc. (Business Wire) discussing research presented at the 2015 CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference, New York] Press Release

Nektar Presents Data Demonstrating that NKTR-214, a CD122-Biased Immunostimulatory Cytokine, Induces Durable and Specific Anti-Tumor Immunity as a Single-Agent and When Combined with Checkpoint Inhibitors in Preclinical Models
Nektar Therapeutics announced positive preclinical results for NKTR-214, a CD122-biased cytokine designed to preferentially stimulate the production and maintenance of tumor-killing T cells which are found naturally in the body. [Press release from Nektar Therapeutics discussing research presented at the 2015 CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference, New York] Press Release

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Bristol-Myers Squibb and Moffitt Cancer Center Enter into a Collaboration Agreement as Part of U.S. Immuno-Oncology Rare Population Malignancy Program
Bristol-Myers Squibb Company and Moffitt Cancer Center announced that they have entered into a collaboration agreement as part of Bristol-Myers Squibb’s Immuno-Oncology Rare Population Malignancy program in the U.S. [Bristol-Myers Squibb Company] Press Release

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