Immune Regulation News Volume 8.09 | Mar 11 2016

A Molecular Threshold for Effector CD8⁺ T Cell Differentiation Controlled by Transcription Factors Blimp-1 and T-Bet
Using genetic approaches and transcriptional profiling of antigen-specific CD8⁺ T cells, the authors revealed a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. [Nat Immunol] Abstract

Itk Is Required for Th9 Differentiation via TCR-Mediated Induction of IL-2 and IRF4
Researchers showed that Itk, a mediator of T cell receptor signaling required for Th2 immune responses and the development of asthma, is a positive regulator of Th9 differentiation. In a model of allergic lung disease, Itk-deficient mice show reduced pulmonary inflammation and interleukin (IL)-9 production by T cells and innate lymphoid type 2 cells (ILC2), despite normal early induction of ILC2s. [Nat Commun] Full Article

Autoantibody-Boosted T-Cell Reactivation in the Target Organ Triggers Manifestation of Autoimmune CNS Disease
Researchers report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. [Proc Natl Acad Sci USA] Abstract

Sialic Acid-Modified Antigens Impose Tolerance via Inhibition of T-Cell Proliferation and De Novo Induction of Regulatory T Cells
Scientists demonstrated that modification of antigens with sialic acids (Sia-antigens) regulates the generation of antigen-specific regulatory T cells via dendritic cells (DCs). Additionally, DCs that take up Sia-antigen prevent formation of effector CD4⁺ and CD8⁺ T cells. [Proc Natl Acad Sci USA] Abstract | Full Article

The Adhesion Molecule PECAM-1 Enhances the TGF-β–Mediated Inhibition of T Cell Function
Researchers found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitated noncanonical (Smad-independent) transforming growth factor–β (TGF-β) signaling in T cells. [Sci Signal] Abstract | Editorial

Intralymphatic mRNA Vaccine Induces CD8 T-Cell Responses that Inhibit the Growth of Mucosally Located Tumors
Scientists demonstrated that E7-TriMix mRNA vaccine-induced CD8⁺ T lymphocytes migrate into the tumor nest and control tumor growth, although they do not express mucosa-associated markers such as CD103 or CD49a. They also showed that despite the presence of the antigen-specific T cells in the tumor lesions, the therapeutic outcomes in the genital tract model remain limited. [Sci Rep] Full Article

NAD⁺ Regulates Treg Cell Fate and Promotes Allograft Survival via a Systemic IL-10 Production that Is CD4⁺ CD25⁺ Foxp3⁺ T Cells Independent
Scientists investigated the impact of NAD⁺ on the fate of CD4⁺ CD25⁺ Foxp3⁺ Tregs in-depth, dissected their transcriptional signature profile and explored mechanisms underlying their conversion into IL-17A producing cells. [Sci Rep] Full Article

Alkaline Ceramidase 3 Deficiency Aggravates Colitis and Colitis-Associated Tumorigenesis in Mice by Hyperactivating the Innate Immune System
Investigators demonstrated that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C_18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells . [Cell Death Dis] Full Article

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Combination of Lapatinib and Trastuzumab Shrinks HER2 Positive Breast Cancer Significantly in 11 Days after Diagnosis
Approximately a quarter of women with HER2 positive breast cancer, who were treated with a combination of the targeted drugs lapatinib and trastuzumab before surgery and chemotherapy, saw their tumors shrink significantly or even disappear, according to results from a clinical trial. [Press release from The University of Manchester discussing research presented at the 10^th European Breast Cancer Conference (EBCC-10), Amsterdam] Press Release

Biothera Pharmaceuticals to Present Its Phase II Cancer Immunotherapy Data
Biothera Pharmaceuticals Inc. presented data on its Phase II cancer immunotherapy Imprime PGG, the company’s first-in-class, systemically administered beta glucan PAMP (pathogen associated molecular patterning molecule). [Press release from Biothera Pharmaceuticals Inc. discussing research presented at the Molecular Medicine Tri-Conference 2016, San Francisco] Press Release

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Advaxis Truly Personalized Cancer Immunotherapy Moves Forward with Signing of an Exclusive Supply Agreement with Synthetic Genomics for Synthetic DNA
Advaxis, Inc. and SGI-DNA announced that the companies have entered into a five-year exclusive supply agreement. Under the terms of the agreement, SGI-DNA will manufacture for Advaxis synthetic DNA which will be used in Advaxis’ personalized Listeria monocytogenes (Lm)-based immunotherapy, known as MINE™ (My Immunotherapy Neo-Epitopes). [Advaxis, Inc.] Press Release

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