Human Immunology News Volume 6.49 | Dec 11 2018

TOP STORY

Low and Variable Tumor Reactivity of the Intratumoral TCR Repertoire in Human Cancers

Investigators analyzed the intrinsic tumor reactivity of the intratumoral T cell receptor (TCR) repertoire of CD8⁺ T cells in ovarian and colorectal cancer—two tumor types for which T cell infiltrates form a positive prognostic marker. [Nat Med] Abstract

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The IL-15-AKT-XBP1s Signaling Pathway Contributes to Effector Functions and Survival in Human NK Cells

Scientists identified a signaling pathway—involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes—that was activated in response to interleukin 15 (IL-15) in human natural killer (NK) cells. [Nat Immunol] Abstract

A Human-Derived Antibody Targets Misfolded SOD1 and Ameliorates Motor Symptoms in Mouse Models of Amyotrophic Lateral Sclerosis

By screening human memory B cells from a large cohort of healthy elderly subjects, investigators generated a recombinant human monoclonal antibody that selectively bound to misfolded superoxide dismutase 1 (SOD1), but not to physiological SOD1 dimers. [Sci Transl Med] Abstract

Loss of ARHGEF1 Causes a Human Primary Antibody Deficiency

The authors used whole-exome sequencing to identify compound heterozygous mutations in ARHGEF1, resulting in the loss of ARHGEF1 protein expression in two primary-antibody-deficient siblings presenting with recurrent severe respiratory tract infections and bronchiectasis. Both ARHGEF1-deficient patients showed an abnormal B cell immunophenotype, with a deficiency in marginal-zone and memory B cells and an increased frequency of transitional B cells. [J Clin Invest] Abstract | Full Article

Induction of Immunosuppressive Functions and NF-κB by FLIP in Monocytes

Scientists showed that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. [Nat Commun] Full Article

SUMOylation of PCNA by PIAS1 and PIAS4 Promotes Template Switch in the Chicken and Human B Cell Lines

To explore the role for SUMOylation of proliferating cell nuclear antigen (PCNA) in DNA damage tolerance, researchers characterized chicken DT40 and human TK6 B cells deficient in the PIAS1 and PIAS4 small ubiquitin-like modifier E3 ligases. [Proc Natl Acad Sci USA] Abstract

Bone Marrow T Helper Cells with a Th1 Phenotype Induce Activation and Proliferation of Leukemic Cells in Precursor B Acute Lymphoblastic Leukemia Patients

Scientists showed that T helper (Th) cells from bone marrow of pediatric B cell acute lymphoblastic leukemia (BCP-ALL) patients can be attracted and activated by autologous BCP-ALL cells. [Oncogene] Abstract

Microanatomical Dissection of Human Intestinal T-Cell Immunity Reveals Site-Specific Changes in Gut-Associated Lymphoid Tissues over Life

Researchers present an analysis of lymphocyte localization and T cell subset composition across the human gastrointestinal tract including mucosal sites, gut-associated lymphoid tissues, and mesenteric lymph nodes from a total of 68 donors spanning eight decades of life. [Mucosal Immunol] Abstract

Cryopreservation of Primary B Cells Minimally Influences their Signaling Responses

B lymphocytes were isolated from healthy donors and patients with the B cell malignancy chronic lymphocytic leukemia and analyzed by phospho flow using phospho-specific antibodies targeting 20 different protein epitopes. [Sci Rep] Full Article

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Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

Scientists summarize the current understanding of the leukocyte recruitment in general and how this varies in different organs. In particular they focus on neutrophils, as these are the first circulating leukocytes to reach the site of inflammation. [Front Immunol] Full Article

Chimeric Antigen Receptor (CAR) T Therapies for the Treatment of Hematologic Malignancies: Clinical Perspective and Significance

The authors provide expert perspective on the significance and clinical considerations of CAR T cell therapies in order to provide timely information to clinicians about this revolutionary new therapeutic class. [J Immunother Cancer] Full Article

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NIH Gives Feinstein Institute $1.68M to Study Sepsis Therapy

Feinstein Institute for Medical Research Assistant Professor, Monowar Aziz, PhD, received a five-year, $1.68 million R01 grant from the National Institutes of Health (NIH) to examine a protein’s role in increasing inflammation and injury in sepsis to develop new therapies. [Feinstein Institute for Medical Research] Press Release

UC San Diego Researcher Gets $4 Million NCI Award to Study Cancer Drug Resistance, Spread

The National Cancer Institute (NCI) has awarded David Cheresh, PhD, Distinguished Professor and vice chair of Pathology at University of California San Diego School of Medicine, with a $4.2 million Outstanding Investigator Award to continue his research into cancer’s ability to overcome stress, gain drug resistance and metastasize. [University of California San Diego] Press Release

NIH to Spend Up to $20 Million on Search for Alternatives to Fetal Tissue for Research

The National Institutes of Health (NIH) wants to fund up to $20 million worth of research into alternatives to using human fetal tissue to study disease, the agency announced. [STAT News] Editorial

Lawsuit Alleges NIH, FDA Let Clinical Trial Sponsors Off the Hook

A former top official at the Food and Drug Administration and a longtime science journalist are suing the agency and the National Institutes of Health (NIH), saying they let clinical trial sponsors off the hook for reporting nearly a decade’s worth of important scientific data. [STAT News] Editorial

Despite Growing Budget, U.S. Cancer Institute Slashes Operating Budget by 5%

A good year for biomedical research funding has turned sour at the National Cancer Institute (NCI) in Bethesda, Maryland, where the director is cutting operating budgets by 5% across the agency. Despite a rising overall budget, NCI’s funds are being stretched thin by various priorities and a ballooning number of funding applications, explains NCI Director Norman “Ned” Sharpless. [ScienceInsider] Editorial

NEW International Conference on Cellular Therapies: Focus on Immune Based Therapeutic Concepts
September 20-22, 2019
Mandelieu, France

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

NEW Research Technologist – Immunology (STEMCELL Technologies Inc.)

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

Supervisor – Transfusion Medicine – Immune, Progenitor, & Cell Therapy (Mayo Clinic)

Postdoctoral Researcher – Epidemiology/Data Science – Immunology, Inflammation and Aging (German Center for Neurodegenerative Diseases)

PhD Position – Cellular and Molecular Determinants of T Cell Responses to CMV Infection (Helmholtz-Center for Infection Research)

Postdoctoral Position – Natural Killer Cells (The Scripps Research Institute)

Postdoctoral/Staff Scientist – Immune Recognition and Immune Tolerance (Boston Children’s Hospital)

Junior Principal Investigator – Cancer Immunity (University of Oxford)

Associate Professor/Professor – Immunobioengineering, Regenerative Medicine or Computational Bioengineering (University of Toronto)

Postdoctoral Fellow – Host Cell-Mediated Immunity (Temple University School of Medicine)

Tenure/Tenure Track Faculty Position – Immunology (Wayne State University)

Postdoctoral Fellowship – Immunology (University of Nantes)

Postdoctoral Fellow – Foxp3+ T-Regulatory in Autoimmunity and Transplantation (Children’s Hospital of Philadelphia)

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