Immune Regulation News Volume 11.07 | Mar 1 2019

TOP STORY

NR4A Transcription Factors Limit CAR T Cell Function in Solid Tumors

To investigate the function of CAR T cells in solid tumors, scientists transferred human CD19 (hCD19)-reactive CAR T cells into hCD19⁺ tumor-bearing mice. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer

Profiling metabolite exchange, researchers demonstrated that macrophages programmed by pancreatic ductal adenocarcinoma cells release a spectrum of pyrimidine species. These include deoxycytidine, which inhibits gemcitabine through molecular competition at the level of drug uptake and metabolism. [Cell Metab] Abstract | Graphical Abstract

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches

The authors used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. They identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. [Immunity] Abstract | Graphical Abstract

CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis

Investigators identified a long non-coding RNA (lnc)-Dpf3 whose feedback restrained CCR7-mediated dendritic cell migration. CCR7 stimulation upregulated lnc-Dpf3 via removing N6-methyladenosine modification to prevent RNA degradation. [Immunity] Abstract | Graphical Abstract

Mitochondrial Hypoxic Stress Induces Widespread RNA Editing by APOBEC3G in Natural Killer Cells

The authors showed that the related cytidine deaminase, APOBEC3G, induced site-specific C-to-U RNA editing in natural killer cells, lymphoma cell lines, and, to a lesser extent, CD8-positive T cells upon cellular crowding and hypoxia. [Genome Biol] Full Article

Increased Intratumoral Mast Cells Foster Immune Suppression and Gastric Cancer Progression through TNF-α-PD-L1 Pathway

Intratumoral mast cells expressed higher immunosuppressive molecule programmed death-ligand 1 (PD-L1), and mast cells induced by tumors strongly expressed PD-L1 proteins in both time-dependent and dose-dependent manners. [J Immunother Cancer] Full Article

The N-Terminal Domain of cGAS Determines Preferential Association with Centromeric DNA and Innate Immune Activation in the Nucleus

Researchers identified determinants of nuclear cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) localization and activation. They showed that nuclear-localized cGAS synthesized cGAMP and induced innate immune activation of dendritic cells, although cGAMP levels were 200-fold lower than following transfection with exogenous DNA. [Cell Rep] Full Article | Graphical Abstract

Immunometabolism Regulates TCR Recycling and iNKT Cell Functions

When the authors characterized the metabolic activity of invariant natural killer T (iNKT) cells, consistent with their activated phenotype, they found that they had much less mitochondrial respiratory capacity but increased glycolytic activity in comparison to naïve conventional CD4⁺ T cells. [Sci Signal] Abstract

Regulation of Cathepsin E Gene Expression by the Transcription Factor Kaiso in MRL/lpr Mice Derived CD4⁺ T Cells

To identify new methylation-sensitive genes, investigators integrated genome-wide DNA methylation and mRNA profiling data in CD4⁺ cells of MRL/lpr and C57BL6/J mice. [Sci Rep] Full Article

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Immunometabolism and Natural Killer Cell Responses

The authors describe the current understanding of mouse and human natural killer (NK) cell metabolism and the key signaling pathways that mediate metabolic responses in NK cells. [Nat Rev Immunol] Abstract

Antigen-Specific Therapeutic Approaches for Autoimmunity

The main function of the immune system in health is to protect the host from infection by microbes and parasites. Because immune responses to nonself bear the risk of unleashing accidental immunity against self, evolution has endowed the immune system with central and peripheral mechanisms of tolerance, including regulatory T and B cells. [Nat Biotechnol] Full Article

Immune Mechanisms of Salt-Sensitive Hypertension and Renal End-Organ Damage

Striking phenotypic similarities have been observed in the infiltration of immune cells in the kidney and the development of end-organ damage in patients and animal models with sodium-sensitive hypertension. The available data suggest that an initial salt-induced increase in renal perfusion pressure, which is likely independent of immune mechanisms, induces the infiltration of immune cells into the kidney. [Nat Rev Nephrol] Abstract

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

Jounce Therapeutics to Present Data from Its JTX-2011 and JTX-8064 Programs

Jounce Therapeutics, Inc. announced that data from its Phase I/II ICONIC trial, an open label trial evaluating JTX-2011 monotherapy and in combination with nivolumab, will be the subject of two poster presentations. [Press release from Jounce Therapeutics, Inc. discussing research to be presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Calithera Biosciences Announces CB-708 Preclinical Data Presentation

Calithera Biosciences, Inc. announced that preclinical data highlighting the potential of CB-708, the company’s orally bioavailable CD73 inhibitor will be presented in a poster session. [Press release from Calithera Biosciences, Inc. discussing research to be presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Principia Biopharma Presents Phase I Clinical Data from CNS Penetrating BTK Inhibitor Candidate PRN2246/SAR442168

Principia Biopharma Inc. announced the presentation of Phase I clinical data for PRN2246, now known as SAR442168. [Press release from Principia Biopharma Inc. discussing research to be presented at the 2019 American Consortium for Therapy and Research in Multiple Sclerosis (ACTRIMS) Annual Meeting, Dallas] Press Release

Lupus Therapeutics Partners with Takeda on Phase I Trial

The Lupus Research Alliance and its affiliate, Lupus Therapeutics, announced a collaboration with Takeda Pharmaceutical Company Limited to evaluate the investigational biologic TAK-079 as a potential new therapy for lupus in a Phase I trial. [The Lupus Research Alliance (PR Newswire Association LLC.)] Press Release

Equillium Announces Plan to Develop EQ001 for the Treatment of Lupus Nephritis

Equillium, Inc. announced that it plans to develop EQ001 for the treatment of lupus nephritis. Equillium remains on track to initiate the EQUATE Phase Ib/II trial in acute graft-versus-host disease in the first quarter of 2019 and initiate a proof-of-concept trial in severe asthma in the second quarter of 2019. [Equillium, Inc.] Press Release

TG Therapeutics Announces Initiation of Phase I First-in-Human Clinical Trial of Its Anti-CD47/CD19 Bispecific Antibody, TG-1801, in Patients with Relapsed or Refractory B-Cell Lymphoma

TG Therapeutics, Inc. announced the commencement of a Phase I first-in-human trial of TG-1801, the company’s novel first-in-class anti-CD47/CD19 bispecific antibody, in patients with relapsed or refractory B-cell lymphoma. [TG Therapeutics, Inc.] Press Release

NIH Letters Asking about Undisclosed Foreign Ties Rattle U.S. Universities

The National Institutes of Health (NIH) has recently sent letters to dozens of major U.S. research universities asking them to provide information about specific faculty members with NIH funding who are believed to have links to foreign governments that the Bethesda, Maryland–based institute did not know about. [ScienceInsider] Editorial

University of California Breaks Up With Major Publisher Over Research Access Dispute

After months of negotiations, the University of California system has decided not to renew its subscriptions to journals put out by the major publisher Elsevier — a decision that could have big ripple effects for the way that academic research gets read and paid for. [STAT News] Editorial

NEW Keystone Symposia: Neural Environment in Disease: Glial Responses and Neuroinflammation
June 16-20, 2019
Keystone, Colorado, United States

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

NEW Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Tumor Immunology (University of Maryland)

Research Officer – Immunotherapy for Brain Cancer (The Walter and Eliza Hall Institute of Medical Research)

Postdoctoral Fellow – Tumor Immune Evasion (Luxembourg Institute of Health)

Staff Scientist – Immunology (Cellzome GmbH)

Assistant Professor – Translational Cancer Research (Texas Tech University Health Sciences Center El Paso)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

Postdoctoral Fellowship – Cancer Immunology and Immunotherapy (Columbia Center for Translational Immunology)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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