Immune Regulation News Volume 11.11 | Mar 29 2019

TOP STORY

CAR T Cell Trogocytosis and Cooperative Killing Regulate Tumor Antigen Escape

Using mouse models of leukemia, researchers showed that chimeric antigen receptors provoked reversible antigen loss through trogocytosis, an active process in which the target antigen is transferred to T cells, thereby decreasing target density on tumor cells and abating T cell activity by promoting fratricide T cell killing and T cell exhaustion. [Nature] Abstract

(Ranked by impact factor of the journal)

T Cell Stemness and Dysfunction in Tumors Are Triggered by a Common Mechanism

High levels of extracellular potassium constrained T cell effector programs by limiting nutrient uptake, thereby inducing autophagy and reduction of histone acetylation at effector and exhaustion loci, which in turn produced CD8⁺ T cells with improved in vivo persistence, multipotency, and tumor clearance. [Science] Abstract | Press Release | Graphical Abstract

Safeguard Function of PU.1 Shapes the Inflammatory Epigenome of Neutrophils

Scientists conditionally deleted the Spi1 gene, which encodes the myeloid transcription factor PU.1, from neutrophils of mice undergoing fungal infection and then performed comprehensive epigenomic profiling. [Nat Immunol] Abstract

A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils

Investigators examined the roles of dermal conventional dendritic cell (cDC)1s and cDC2s during bacterial infection, notably Propionibacterium acnes. cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. [Immunity] Abstract | Graphical Abstract

Negative Co-Stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States

The authors used mass cytometry to profile T cells generated in the genetic absence of the negative co-stimulatory molecules CTLA-4 and PD-1. They indicated that negative co-stimulation constrained the possible cell states that peripheral T cells can acquire. [Immunity] Abstract | Graphical Abstract

Wnt1 Silences Chemokine Genes in Dendritic Cells and Induces Adaptive Immune Resistance in Lung Adenocarcinoma

Researchers showed that lung adenocarcinoma (LUAD) cells used paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlated strongly with tolerogenic genes. In another LUAD cohort, Wnt1 inversely associated with T cell abundance. [Nat Commun] Full Article

Specialized Dendritic Cells Induce Tumor-Promoting IL-10⁺IL-17⁺ FoxP3^neg Regulatory CD4⁺ T Cells in Pancreatic Carcinoma

Using models of pancreatic ductal adenocarcinoma (PDA), scientists showed that a distinct subset of tumor-infiltrating dendritic cells promoted PDA growth by directing a unique T_H-program. [Nat Commun] Full Article

Nemo-Like Kinase Drives Foxp3 Stability and Is Critical for Maintenance of Immune Tolerance by Regulatory T Cells

Investigators showed that during T cell activation, phosphorylation of Foxp3 in T_REG cells could be regulated by a TGF-β activated kinase 1-Nemo-like kinase signaling pathway. [Cell Rep] Full Article | Graphical Abstract

Bone Marrow-Derived Ly6C⁻ Macrophages Promote Ischemia-Induced Chronic Kidney Disease

The authors found that C-C chemokine receptor type 2 deficiency, which blocks the migration of Ly6C⁺ macrophages from the bone marrow to the sites of injury, alleviated ischemia-induced acute kidney injury in mice. [Cell Death Dis] Full Article

Activation of Death-Associated Protein Kinase 1 Promotes Neutrophil Apoptosis to Accelerate Inflammatory Resolution in Acute Respiratory Distress Syndrome

Researchers investigated whether 5-Aza-2′-deoxycytidine (Aza) could regulate death-associated protein kinase 1 (DAPK1) expression to influence the fate of neutrophils in acute respiratory distress syndrome. In vitro, they stimulated neutrophil-like HL-60 cells with different concentrations of Aza for different durations and used RNA interference to up- or downregulate DAPK1 expression. [Lab Invest] Abstract

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Navigating Metabolic Pathways to Enhance Antitumor Immunity and Immunotherapy

Scientists discuss how metabolic circuits regulate antitumor immunity and the possible approaches to targeting these pathways in the context of anticancer immunotherapy. They also describe hypothetical combination treatments that could be used to better unleash the potential of adoptive cell therapies by enhancing T cell metabolism. [Nat Rev Clin Oncol] Abstract

NK Cell Recognition of Hematopoietic Cells by SLAM-SAP Families

The authors review how two distinct signaling lymphocyte activation molecule (SLAM) family of receptor (SFR) signaling pathways orchestrate NK cell activation and inhibition and highlight the importance of SFR regulation of NK cell biology and their physiological status and pathological relevance in patients with XLP1. [Cell Mol Immunol] Abstract

Targeting Natural Killer Cells in Solid Tumors

Researchers review the current knowledge on the presence and function of natural killer (NK) cells in solid tumors as well as the immunotherapeutic approaches designed to harness NK cell functions in these conditions, including those that aim to reinforce conventional anti-tumor therapies to increase the chances of successful treatment. [Cell Mol Immunol] Abstract

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

Study May Explain Why Immunotherapy not Effective for Some Patients with Metastatic Melanoma and Kidney Cancer

White blood cells known as B cells have been shown to be effective for predicting which cancer patients will respond to immune checkpoint blockade therapy, according to a study. [Press release from The University of Texas MD Anderson Cancer Center discussing research to be presented at the AACR Annual Meeting 2019, Atlanta] Press Release

eFFECTOR Presents Data on its Selective Translation Regulators

eFFECTOR Therapeutics, Inc. announced that data from all three of its pipeline programs – tomivosertib, eFT226 and its eIF4E program – will be presented. [Press release from eFFECTOR Therapeutics, Inc. discussing research to be presented at the AACR Annual Meeting 2019, Atlanta] Press Release

Lilly and ImmuNext Announce Licensing and Research Collaboration

Eli Lilly and Company and ImmuNext, Inc. announced a global licensing and research collaboration focused on the study of a preclinical novel target that could lead to potential new medicines for autoimmune diseases by regulating immune cell metabolism. [Eli Lilly and Company] Press Release

OSE Immunotherapeutics Announces New Research Collaboration with Léon Bérard Cancer Center to Use Artificial Intelligence Technologies to Identify Novel Immuno-Oncology Targets

OSE Immunotherapeutics announced a new research collaboration agreement with Léon Bérard Cancer Center to use artificial intelligence-based bioanalysis and bioinformatics to identify novel targets in immuno-oncology. [OSE Immunotherapeutics] Press Release

Transgene and BioInvent Extend Their Collaboration to Develop Multifunctional Oncolytic Viruses for the Treatment of Solid Tumors

Transgene and BioInvent International AB announcd the extension of their collaboration to co-develop multi-functional oncolytic viruses encoding for undisclosed antibodies sequences capable of treating a broad range of solid tumors. [Transgene SA] Press Release

Akrevia Therapeutics Licenses Exclusive Rights from City of Hope to Expand Development Pipeline of Potent, Tumor Targeted Immunotherapies

Akrevia Therapeutics and City of Hope announced that they have entered into an exclusive licensing agreement that will allow Akrevia to utilize innovative technology to engineer potent immune-activating cytokines that can be selectively activated in the tumor microenvironment. [Akrevia Therapeutics, LLC (PR Newswire Association LLC)] Press Release

Immuno-Oncology Company Elicio Therapeutics Launches with Novel Vaccine & Immunotherapy Platform to Treat an Array of Cancers

Elicio Therapeutics launched and announced the appointment of Robert Connelly as CEO. Elicio is developing precision vaccines, immuno stimulators and cellular therapies based on the ground-breaking work of Darrell Irvine, PhD., Professor of Biological Engineering and Materials Sciences and Howard Hughes Investigator at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. [Elicio Therapeutics] Press Release

Advaxis Granted US Patent Relating to Axalimogene Filolisbac

Advaxis, Inc. announced that the US Patent and Trademark Office has granted patent number 10,189,885 titled “Non-Hemolytic LLO Fusion Proteins and Methods of Utilizing Same.” [Advaxis, Inc. (Business Wire, Inc.)] Press Release

Mallinckrodt Announces 2019 Investigator Award for Pioneering Efforts in ECP Immunomodulation

Mallinckrodt plc announced the recipient of 2019’s Advancing Extracorporeal Photopheresis (ECP) Immunomodulation Investigator Award. The winning entry was submitted by co-investigator Dr. Rachel Crossland of Newcastle University in the United Kingdom. [Mallinckrodt plc] Press Release

University Fights Restrictive Indiana Law on Fetal Tissue Research

A three-judge panel of the Seventh U.S. Circuit Court of Appeals overturned a lower court decision that an Indiana law criminalizing much fetal tissue research is unconstitutionally vague. The ruling moves such work closer to being a felony in the Hoosier State. It’s the most significant court decision yet on laws recently passed in at least seven states that restrict research on tissue from elective abortions. [ScienceInsider] Editorial

NIH May Bar Peer Reviewers Accused of Sexual Harassment

The National Institutes of Health (NIH) in Bethesda, Maryland, reminded the research community this week that the agency can—and sometimes does—bar scientists accused of sexual harassment from serving as peer reviewers. [ScienceInsider] Editorial

NEW International Society for Stem Cell Research (ISSCR) 2019 Annual Meeting
June 26-29, 2019
Los Angeles, California, United States

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

NEW Director of Research – Division of Translational Medicine & Human Genetics (University of Pennsylvania)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Innate Lymphoid Cell Biology (Karolinska Institutet)

Postdoctoral Fellow – Immuno-Oncology (Georgetown Lombardi Comprehensive Cancer Center)

Faculty Position – Immunology (Fox Chase Cancer Center)

Research Fellow – Protective and Aberrant Immunity (Monash University)

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

Postdoctoral Fellow – Tumor Immunology (University of Maryland)

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)

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

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