Immune Regulation News Volume 9.23 | Jun 23 2017

TOP STORY

De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation

Investigators report that blocking de novo DNA methylation in activated CD8 T cells allows them to retain their effector functions despite chronic stimulation during a persistent viral infection. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

ITK Signaling via the Ras/IRF4 Pathway Regulates the Development and Function of Tr1 Cells

Scientists showed that ITK, an important modulator of T cell receptor (TCR) signaling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. [Nat Commun] Full Article

CTLA-4-Mediated Posttranslational Modifications direct Cytotoxic T-Lymphocyte Differentiation

The authors discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 as a result of FoxO1 nuclear re-localization. [Cell Death Differ] Full Article

Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells

Using precursor/product relationships, researchers identified thymic stages in two distinct developmental pathways that generated γδ T cells pre-committed to subsequent secretion of either IL-17A or IFNγ. [Cell Rep] Full Article | Graphical Abstract

Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8⁺ T Cell Responses Independently of Transgene Expression in Dendritic Cells

Scientists report that intradermal immunization with a model recombinant adeno-associated viral (rAAV)2/1-based vaccine drives the development of bona fide long-term memory CD8⁺ T cell responses. [Mol Ther] Abstract

A Novel and Effective Method to Generate Human Porcine-Specific Regulatory T Cells with High Expression of IL-10, TGF-β1 and IL-35

Researchers demonstrated the use of a fast method to provide tolerogenic dendritic cells (tolDC) that could be used to generate effective porcine-specific Treg cells. TolDC were produced within three days from human monocytes in medium supplemented with anti-inflammatory cytokines. [Sci Rep] Full Article

TGF-Beta/atRA-Induced Tregs Express a Selected Set of MicroRNAs Involved in the Repression of Transcripts Related to Th17 Differentiation

Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4_Med) or with the addition of TGF-β and atRA (CD4_TGF/atRA). As compared to CD4_Med, the CD4_TGF/atRA condition allowed the generation of highly suppressive CD4⁺CD25^hiCD127⁻FOXP3^hi iTregs. [Sci Rep] Full Article

Hepatic Stroma-Educated Regulatory DCs Suppress CD8⁺ T Cell Proliferation in Mice

Investigators found that bone marrow-derived mature dendritic cells (DCs) incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. [Oncotarget] Full Article

Antigen Availability and DOCK2-Driven Motility Govern CD4⁺ T Cell Interactions with Dendritic Cells In Vivo

Using intravital imaging of reactive lymph nodes in dendritic cell (DC)-immunized mice, scientists showed that peptide-MHC (pMHC) levels determined the occurrence and timing of stable CD4⁺ T cell–DC interactions. Despite the variability in interaction parameters, ensuing CD4⁺ T cell proliferation was comparable over a wide range of pMHC levels. [J Immunol] Abstract

Loss of IP₃ Receptor–Mediated Ca²⁺ Release in Mouse B Cells Results in Abnormal B Cell Development and Function

The authors generated a B cell–specific inositol 1,4,5-trisphosphate receptor (IP₃R) triple-knockout mouse model and revealed that loss of IP₃Rs increased transitional B cell numbers and reduced recirculating mature B cell numbers in bone marrow. [J Immunol] Abstract

Memory-Phenotype CD4⁺ T Cells Spontaneously Generated under Steady-State Conditions Exert Innate T_H1-Like Effector Function

Investigators showed that memory-phenotype cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a T cell receptor– and CD28-dependent manner. [Sci Immunol] Abstract

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T Follicular Regulatory Cells in Mice and Men

Investigators review the biology and function of the recently described T follicular regulatory cells, another CD4 T cell population also found within germinal centers but with regulatory function and characteristics. [Immunology] Abstract

mTORC1 and mTORC2 as Regulators of Cell Metabolism in Immunity

The authors focus on the role of the mechanistic target of rapamycin complex (mTORC)1 and mTORC2 in the regulation of the cellular energy metabolism of these immune cells to regulate and support immune responses. [FEBS Lett] Abstract

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

TCR(2) Therapeutics Presents Positive Solid Tumor Data for its Novel TRuC™ Engineered T Cell Therapies

TCR² Therapeutics Inc. announced data on two of its TRuC™ programs that showed superior persistence and anti-tumor activity of the company’s TRuC™-T cells compared to CAR-T cells in preclinical models. [Press release from TCR² Therapeutics Inc. discussing research presented at the World Preclinical Congress (WPC), Boston] Press Release

Dose-Escalation Data Show Favorable Safety Profile and Promising Clinical Activity for IPH4102

Innate Pharma SA announced results from the dose-escalation part of the ongoing Phase I study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas, an orphan disease. [Press release from Innate Pharma SA discussing research presented at the International Conference on Malignant Lymphoma (ICML), Lugano] Press Release

Unum Therapeutics Announces Active Investigational New Drug (IND) Application for ACTR707 in Combination with Rituximab in Patients with Relapsed/Refractory B-Cell Lymphoma

Unum Therapeutics announced that an IND application for ACTR707 in combination with rituximab for the treatment of adult patients with relapsed/refractory CD20-positive B cell non-Hodgkin lymphoma, is now active. [Unum Therapeutics Inc.] Press Release

Genexine Receives Approval to Initiate Phase Ib/II Trial of GX-188E, HPV Therapeutic DNA Vaccine, in Combination with KEYTRUDA^® (Pembrolizumab), for the Treatment of HPV-Induced Cervical Cancer

Genexine Inc. announced that the Ministry of Food and Drug Safety in Korea has granted approval to initiate a Phase Ib/II trial of GX-188E, an HPV therapeutic DNA vaccine, in combination with KEYTRUDA^®, an anti-PD-1 therapy for the treatment of patients with HPV-induced advanced non-resectable cervical cancer. [Genexine, Inc.] Press Release

Leap Therapeutics Announces Collaboration with Merck to Evaluate KEYTRUDA^® (Pembrolizumab) in Combination with DKN-01 in Esophagogastric Cancer

Leap Therapeutics, Inc. announced that it has entered into a clinical trial collaboration agreement with Merck to investigate Leap’s DKK1 antagonist, DKN-01, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^®, in patients with relapsed or refractory advanced esophagogastric cancers. [Leap Therapeutics, Inc.] Press Release

Adaptive Biotechnologies Announces a Collaboration with Janssen Biotech, Inc. to Use the clonoSEQ^® Assay to Measure Minimal Residual Disease in Ongoing and Future DARZALEX^® Multiple Myeloma Trials

Adaptive Biotechnologies announced it has partnered with Janssen Biotech, Inc. to utilize Adaptive’s next generation sequencing-based clonoSEQ Assay for measuring minimal residual disease in patients with multiple myeloma who have been treated with DARZALEX. [Adaptive Biotechnologies] Press Release

US Court Grants Elsevier Millions in Damages from Sci-Hub

One of the world’s largest science publishers, Elsevier, won a default legal judgement against websites that provide illicit access to tens of millions of research papers and books. A New York district court awarded Elsevier US$15 million in damages for copyright infringement by Sci-Hub, the Library of Genesis project and related sites. [Nature News] Editorial

University of Tokyo Scientist Hit by Anonymous Allegations Fights Back

Anonymous allegations of questionable data and images in 22 papers by six prominent groups at the prestigious University of Tokyo prompted the school to set up an investigating committee. Now, even before the panel completes its investigation, one of the accused researchers has mounted a staunch defense of his work. [ScienceInsider] Editorial

China Cracks Down on Fake Peer Reviews

The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. [Nature News] Editorial

Strengthened US Sanctions on Cuba Disappoint Scientists

US President Donald Trump announced that he would strengthen travel and trade restrictions against Cuba, reversing his predecessor’s attempts to normalize relations with the country. The move is a blow to scientists who hoped that former president Barack Obama’s push to relax US restrictions on Cuba would make it easier for researchers there to travel and to collaborate with colleagues in the United States. [Nature News] Editorial

NEW AACR-NCI-EORTC Molecular Targets & Cancer Therapeutics
October 26-30, 2017
Philadelphia, Pennsylvania, United States

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NEW Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Scientific Sales Representative – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Scientist – Immunogenomics (University of Oxford)

Scientist – Neuroinflammation (University Health Network)

Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (VIB-KU Leuven Center for Cancer Biology)

Postdoctoral Fellow – Neuroimmunology (The University of Texas MD Anderson Cancer Center)

Immunologist – Brain Cancer (Columbia University)

Postdoctoral Position – Cancer Immunology and Immunotherapy (Weill Cornell Medicine)

Scientist I – T Cell Immunology (Celgene Corporation)

Scientist – Analytical Development (KBI Biopharma)

Senior Scientist – Molecular and Cellular Neuroimmunology (Pfizer)

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

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