Immune Regulation News Volume 9.35 | Sep 15 2017

TOP STORY

Enhancing CD8⁺ T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy

Scientists report that CD8⁺ tumor-infiltrating T lymphocytes enhance peroxisome proliferator-activated receptor-α signaling and catabolism of fatty acids when simultaneously subjected to hypoglycemia and hypoxia. [Cancer Cell] Abstract

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Tumor Lymphangiogenesis Promotes T Cell Infiltration and Potentiates Immunotherapy in Melanoma

Investigators found that vascular endothelial growth factor–C (VEGF-C) signaling enhanced rather than suppressed the response to immunotherapy. They found that this effect was mediated by VEGF-C–induced CCL21 and tumor infiltration of naïve T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C. [Sci Transl Med] Abstract | Press Release

Selective Degradation of PU.1 during Autophagy Represses the Differentiation and Antitumor Activity of T_H9 Cells

Scientists showed that autophagy selectively represses T helper 9 (T_H9) cell differentiation. CD4 T cells lacking Atg3 or Atg5 have increased interleukin-9 expression upon differentiation into T_H9 cells relative to Atg3– or Atg5-expressing control cells. [Nat Commun] Full Article

Tia1 Dependent Regulation of mRNA Subcellular Location and Translation Controls p53 Expression in B Cells

The authors describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. [Nat Commun] Full Article

B Cell–Derived IL-6 Initiates Spontaneous Germinal Center Formation during Systemic Autoimmunity

Investigators report the finding that a lack of B cell–derived IL-6 abrogates spontaneous germinal center formation in mouse systemic lupus erythematosus, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. [J Exp Med] Abstract

Self-Transducible Bimodal Pdx1-Foxp3 Protein Rescues Insulin Secretion and Curbs Autoimmunity Boosting Treg Cells in Type 1 Diabetic Mice

In vitro, fusion protein converted naïve CD4⁺ T cells into the functional “Treg-like” subset, which suppressed cytokine secretion, down-regulated antigen-specific responses, and curbed viability of diabetogenic effector cells. [Mol Ther] Abstract

Multipeptide-Coupled Nanoparticles Induce Tolerance in ‘Humanized’ HLA-Transgenic Mice and Inhibit Diabetogenic CD8⁺ T Cell Responses in Type 1 Diabetes

The authors showed that peptides-polystyrene beads could induce antigen-specific tolerance in HHD II mice. The protective immunological mechanisms were mediated through the function of CD4⁺CD25⁺ regulatory T cells, suppressive T cell activation and T cell anergy. [Diabetologia] Abstract

Casein Kinase 2 Is a Critical Determinant of the Balance of Th17 and Treg Cell Differentiation

Researchers demonstrated that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro. [Exp Mol Med] Full Article

Extracellular Vesicles Derived from T Regulatory Cells Suppress T Cell Proliferation and Prolong Allograft Survival

Investigators document that dnIKK2-Treg release extracellular vesicles (EV) riched in exosomes, fully accounting for the cell-contact independent immunosuppressive activity of parent cells. DnIKK2-Treg-EV contain a unique molecular cargo of specific miRNAs and iNOS, which, once delivered into target cells, blocked cell cycle progression and induced apoptosis. [Sci Rep] Full Article

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Regulatory T-Cell Heterogeneity and the Cancer Immune Response

Treg heterogeneity likely affects predictions of patient outcome, and different Treg populations may have different influences on tumors. The study of Tregs in cancer must include a better definition of the cells analyzed. The authors focus primarily on colorectal cancer in humans, due to mixed data on the impact of Tregs on patient outcome in this disease. [Clin Transl Med] Abstract

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

UCLA Opens First Engineered Blood Stem Cell Clinical Trial for Cancers with the NY-ESO-1 Tumor Marker

Scientists have initiated a Phase I clinical trial to test a novel cancer treatment for certain kinds of cancers that have a specific tumor marker called NY-ESO-1. [Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research] Press Release

Merck ‘Grant for Oncology Innovation’ Awards Recognize Recipients for Pushing Boundaries in Oncology Research

Merck announced recipients of the fourth annual Grant for Oncology Innovation awards. The three winners of this prestigious program were awarded €1 million in total to progress their research. [Merck KGaA (PR Newswire Association LLC)] Press Release

SELLAS’ Galinpepimut-S Induces Specific, Robust and Durable Immune Responses in Patients with High-Risk Multiple Myeloma – Correlated with Clinical Benefit

SELLAS Life Sciences Group Ltd. reported that its WT1-targeting immuno-oncology treatment, galinpepimut-S, led to mounting of specific, potent and durable immune responses in multiple myeloma patients. [SELLAS Life Sciences Group Ltd.] Press Release

FDA Approves New Treatment for Adults with Relapsed Follicular Lymphoma

The FDA granted accelerated approval to Aliqopa for the treatment of adults with relapsed follicular lymphoma who have received at least two prior treatments known as systemic therapies. [FDA] Press Release

U.S. House Approves 2018 Spending Bills, but Process Far from Finished

The U.S. House of Representatives took a major step toward setting federal science budgets for the 2018 fiscal year. But Congress is still far from the finish line, and final spending levels aren’t likely to be finalized until late this year at the earliest. [ScienceInsider] Editorial

After Uproar, U.K. Parliament’s Science Committee Now Has a Female Member

The House of Commons Science and Technology Committee tweeted that it was “pleased to announced our membership has been confirmed.” Parliamentary committees had been dissolved after the recent U.K. election, and now the panel was rolling out its new contingent of lawmakers. [ScienceInsider] Editorial

NEW Keystone Symposia: Aging, Inflammation and Immunity
February 25-March 1, 2018
Austin, Texas, United States

Visit our events page to see a complete list of events in the community.

NEW Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

NEW Scientist – Immunology (STEMCELL Technologies Inc.)

NEW Research Scientist – Immuno-Oncology (Kymab Ltd)

Postdoctoral Researcher – Development of Immune System (Lund University)

Assistant Professor – Protective Immunity (Children’s Hospital of Philadelphia)

Postdoctoral Research Associate – Mega Proteins to Control T Cell Signaling (University of Oxford)

Postdoctoral Training Fellows – Cell Death & Inflammation (Institute of Cancer Research)

Postdoctoral Fellowship – Immunology (University of Georgia)

Postdoctoral Research Fellows – Systems Immunology (University of Oslo)

Postdoctoral Scholar – Regulation of Immune Responses (University of Iowa)

Postdoctoral Fellowships – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

Research Fellow Position – Immunology Research (ShanghaiTech University)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte Ltd.)

Postdoctoral Researcher – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

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