Human Immunology News Volume 6.09 | Mar 6 2018

TOP STORY

Researchers Identify Renegade Cells that Portend Relapse in Children with Leukemia

Researchers have developed a technique that allowed them to determine at diagnosis whether children with acute lymphoblastic leukemia would relapse following treatment. The method predicted relapse in the cohort they examined with 85 percent accuracy, a significant improvement from 66 percent accuracy achieved by the current risk stratification method used at diagnosis. [Press release from the Stanford University School of Medicine discussing online prepublication in Nature Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8⁺ T Cells

Scientists found that rapid activation of protein kinase B by mammalian target of rapamycin complex 2 led to inhibition of glycogen synthase kinase 3β at mitochondria-endoplasmic reticulum junctions. This enabled recruitment of hexokinase I to the voltage-dependent anion channel on mitochondria. [Immunity] Abstract | Graphical Abstract

HIV Latency in Isolated Patient CD4⁺ T Cells May Be Due to Blocks in HIV Transcriptional Elongation, Completion, and Splicing

Investigators developed a new panel of reverse transcription droplet digital polymerase chain reaction assays specific for different HIV transcripts that define distinct blocks to transcription. They applied this panel of assays to CD4⁺ T cells freshly isolated from HIV-infected patients on suppressive antiretroviral therapy to quantify the degree to which different mechanisms inhibit HIV transcription. [Sci Transl Med] Abstract | Press Release

Adoptive Cancer Immunotherapy Using DNA-Demethylated T Helper Cells as Antigen-Presenting Cells

Scientists report that activated CD4⁺ T helper cells treated with a DNA-demethylating agent expressed a broad repertoire of endogenous cancer/testis antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes and natural killer cells. [Nat Commun] Full Article

CRISPR RNAs Trigger Innate Immune Responses in Human Cells

Researchers showed that the triphosphate group can be removed by a phosphatase in vitro and that the resulting 5′-hydroxyl guide RNAs in complex with Cas9 or Cpf1 avoid innate immune responses and can achieve targeted mutagenesis at a frequency of 95% in primary human CD4⁺ T cells. [Genome Res] Full Article

Indoleamine 2,3-Dioxygenase Expression Regulates the Survival and Proliferation of Fusobacterium nucleatum in THP-1-Derived Macrophages

Scientists determined the molecular mechanisms underlying the morphology, survival, and proliferation of F. nucleatum (Fn) in THP-1-derived macrophages (dTHP1). They found that Fn is a facultative intracellular bacterium that can survive and limited proliferate in dTHP1 cells up to 72 hours, and a live Fn infection can inhibit apoptosis of dTHP1 cells by activating the PI3K and ERK pathways. [Cell Death Dis] Full Article

Peptide-MHC Class I Tetramers Can Fail to Detect Relevant Functional T Cell Clonotypes and Underestimate Antigen-Reactive T Cell Populations

Investigators used several viral- and tumor-specific peptide-MHC (pMHC) reagents to compare populations of human T cells stained by standard pMHC protocols and optimized protocols that they developed. They confirm that optimized protocols recover greater populations of T cells that include fully functional T cell clonotypes that cannot be stained by regular pMHC-staining protocols. [J Immunol] Abstract | Full Article

Next Generation Sequencing Reveals Changes of the γδ T Cell Receptor Repertoires in Patients with Pulmonary Tuberculosis

The authors found a preponderant complementarity-determining region 3 sequence of the γδ T cell receptor in tuberculosis patients, and successfully identified a tuberculosis antigen that can effectively activate γδ T cells with a reverse genetic strategy. [Sci Rep] Full Article

Allogeneic Dendritic Cells Stimulated with Antibodies against HLA Class II Polarize Naive T Cells in a Follicular Helper Phenotype

Investigators demonstrated that human allogeneic dendritic cells stimulated with antibodies against HLA class II antigens preferentially differentiate human naive CD4⁺ T cells into follicular helper T cells. [Sci Rep] Full Article

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Lessons Learned from the Blockade of Immune Checkpoints in Cancer Immunotherapy

Scientists summarize the current understanding of the mechanisms by which resistance to checkpoint blockade immunotherapy occurs, and outline how actionable combination strategies may be derived to improve clinical outcomes for patients. [J Hematol Oncol] Full Article

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Aduro Announces Milestone Achieved under Merck Collaboration for Initiation of Anti-CD27 Phase I Trial in Advanced Solid Tumors

Aduro Biotech, Inc. announced that the company earned a $3.0 million development milestone payment under its worldwide licensing agreement with Merck for the initiation of a Phase I clinical trial of its anti-CD27 antibody. [Aduro Biotech, Inc.] Press Release

Sorrento Therapeutics Autologous Anti-CEA CAR-T Cell Therapy for Liver Metastases Demonstrates Therapeutic Activity in Stage IV Pancreas Cancer in a Phase Ib HITM-SURE Trial (NCT02850536)

Sorrento Therapeutics, Inc., TNK Therapeutics, Inc. and Surefire Medical, Inc. announced initial results from the Hepatic ImmunoTherapy for Metastases-Surefire, or HITM-SURE, a Phase Ib single arm trial testing its autologous anti-CEA CAR-T cells administered regionally by hepatic artery infusion via pressure directed microvalve infusion technology in heavily pre-treated patients with refractory CEA-positive liver metastases. [Sorrento Therapeutics, Inc.] Press Release

New NSF Rules on Sexual Harassment Leave Many Questions Unanswered

The National Science Foundation (NSF) in Alexandria, Virginia, hopes that its new policy on sexual harassment will spur universities to deal more aggressively with the pervasive problem. But the additional reporting requirements, which will be officially published in the Federal Register, are far from a definitive statement about how NSF plans to deal with this complex and sensitive subject. [ScienceInsider] Editorial

EU Research Chief’s Next Act: Changing the Future of Academic Publishing

Robert-Jan Smits, one of Europe’s most powerful figures in research, has been appointed as a special envoy on open science at the European Commission, to help push efforts to make all publicly funded research in Europe freely available by 2020. [Science|Business] Editorial

Indian Scientist’s Sacking Spotlights Sexual Harassment

Female scientists in India hope that more academics will report sexual harassment without fear of jeopardizing their career or reputation, after a prominent biologist was sacked for allegedly harassing a staff member. [Nature News] Editorial

NEW Gordon Research Conferences: Immunochemistry and Immunobiology
June 10-15, 2018
West Dover, Vermont, United States

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NEW Postdoctoral Position – Immune Oncology (H. Lee Moffitt Cancer & Research Institute)

NEW Scientist – Immune Tolerance (Moderna Therapeutics)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

Postdoctoral Research Associate – Immunity and Inflammation (University of Illinois)

Principal Scientist – Immunosciences Drug Discovery (Bristol-Myers Squibb)

Postdoctoral Fellow – T-Cell Therapy (Memorial Sloan Kettering Cancer Center)

PhD Studentship – Treg Cell Research (Universitätsklinikum Carl-Gustav-Carus Dresden)

Postdoctoral Scientist Opportunities – Biomedical Research (Cedars-Sinai)

Senior Director – Immuno-Oncology Research (Alector LLC)

Postdoctoral Fellow – Immunology/Vascular/Stromal Biology (Hospital for Special Surgery and Weill Cornell Medicine)

Head of Laboratory – Cancer Vaccines/Oncolytic Viruses (Boehringer Ingelheim)

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