Human Immunology News Volume 6.32 | Aug 14 2018

TOP STORY

Exosomal PD-L1 Contributes to Immunosuppression and Is Associated with Anti-PD-1 Response

Researchers report that metastatic melanomas release extracellular vesicles, mostly in the form of exosomes, that carry programmed death-ligand 1 (PD-L1) on their surface. Stimulation with interferon-γ increases the amount of PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumor growth. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Generation of Tumor-Reactive T Cells by Co-Culture of Peripheral Blood Lymphocytes and Tumor Organoids

The authors demonstrated that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. [Cell] Abstract

Sequestration of T Cells in Bone Marrow in the Setting of Glioblastoma and other Intracranial Tumors

Investigators revealed that even treatment-naïve subjects and mice with glioblastoma can harbor AIDS-level CD4 counts, as well as contracted, T cell-deficient lymphoid organs. Missing naïve T cells were instead found sequestered in large numbers in the bone marrow. [Nat Med] Abstract | Press Release

Anti-CD37 Chimeric Antigen Receptor T Cells Are Active against B and T Cell Lymphomas

Scientists found that chimeric antigen receptor-37 T cells demonstrated antigen-specific activation, cytokine production, and cytotoxic activity in models of B- and T-cell lymphomas in vitro and in vivo, including patient-derived xenografts. [Blood] Abstract

Molecular Mechanisms of Autophagic Memory in Pathogenic T Cells in Human Arthritis

Researchers demonstrated “autophagic memory” as elevated autophagy levels in CD4⁺ memory T cells compared to CD4⁺ naive T cells and in jurkat human T cell line trained with starvation stress. [J Autoimmun] Full Article

Treatment-Naïve HPV⁺ Head and Neck Cancers Display a T-Cell-Inflamed Phenotype Distinct from Their HPV- Counterparts that Has Implications for Immunotherapy

Using TCGA data, investigators compared the immune landscape between human papillomavirus (HPV)⁺ and HPV^– treatment-naïve head and neck squamous cell carcinoma. [OncoImmunology] Full Article

Engineering of Primary Human B Cells with CRISPR/Cas9 Targeted Nuclease

Researchers report optimized CRISPR/Cas9 based genome engineering of primary human B cells. The procedure involved enrichment of CD19⁺ B cells from PBMCs followed by activation, expansion, and electroporation of CRISPR/Cas9 reagents. [Sci Rep] Full Article

TNFR2 Ligation in Human T Regulatory Cells Enhances IL2-Induced Cell Proliferation through the Non-Canonical NF-κB Pathway

RNA-seq analysis of TNF- or D18-treated human T regs revealed that TNFR2 ligation induces transcription of NFKB2 and RELB, encoding proteins that form the non-canonical NF-κB transcription factor. [Sci Rep] Full Article

Immune Surveillance by Autoreactive CD4 Positive Helper T-Cells Is a Common Phenomenon in Patients with Acute Myeloid Leukemia

Investigators demonstrated that acute myeloid leukemia-induced autoreactivity was predominantly mediated by CD4 T-cells. These auto-reactive T-cells showed abundant cytokine production, coincided by modest cytotoxic activity. [Eur J Haematol] Abstract

Quantifying Size and Diversity of the Human T Cell Alloresponse

Researchers present a statistical method to model T cell clonal frequency distribution and quantify repertoire diversity. Using these approaches, they measured the diversity and frequency of distinct alloreactive CD4⁺ and CD8⁺ T cell populations in HLA-mismatched responder-stimulator pairs. [JCI Insight] Full Article

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The Impact of Inflationary CMV-Specific Memory T Cells on Anti-Tumor Immune Responses in Patients with Cancer

Researchers review “memory T-cell inflation” phenomenon and associated factors including age and sex. ‘Collateral damage’ due to cytomegalovirus (CMV)-directed immune reactivity may occur in later stages of life – arising from CMV-specific immune responses that were beneficial in earlier life. [Immunology] Abstract | Full Article

Visit our reviews page to see a complete list of reviews in the human immunology research field.

Solid Tumors Targeted in New CAR T-Cell Immunotherapy Trial

Seattle Children’s has opened a chimeric antigen receptor (CAR) T-cell immunotherapy trial for children and young adults with relapsed or refractory non-central nervous system EGFR-expressing solid tumors. In the Phase I trial, STRIvE-01, cancer-fighting CAR T cells will target the EGFR protein expressed in many childhood sarcoma, kidney and neuroblastoma tumors. [Seattle Children’s] Press Release

Researcher Investigates New Way to Fight Bacterial Pneumonia; Nervous System May Play Role

Dr. Bryan Yipp, MD, and Dr. Christophe Altier, PhD, member of the CSM’s Snyder Institute for Chronic Diseases, the Hotchkiss Brain Institute and the Alberta Children’s Hospital Research Institute are using animal models to see what is occurring at a molecular level between the nervous system and the immune system. [University of Calgary] Press Release

Unum Therapeutics Announces Active Investigational New Drug (IND) Application for Antibody-Coupled T Cell Receptor (ACTR) Platform in Combination with Trastuzumab in Patients with HER2⁺ Advanced Cancers

Unum Therapeutics Inc. announced that an IND application is now active for ACTR T cells in combination with trastuzumab for the treatment of patients with HER2⁺ advanced cancers. [Unum Therapeutics Inc.] Press Release

Survey of U.S. Government Scientists Finds Range of Attitudes Toward Trump Policies

It’s widely assumed that many U.S. government scientists disagree with President Donald Trump on several of his controversial science appointments, his proposed deep cuts to research, and a spate of executive actions aimed at overturning current government policies to combat climate change. Some have publicly voiced their concerns. But what do the rank-and-file really think of working for this president? [ScienceInsider] Editorial

US Congress Leaves Science Agencies Hanging — Again

Lawmakers in the US Congress are running out of time to pass a budget for the 2019 fiscal year, and have yet to resolve major disagreements over climate-change and environment programs. [Nature News] Editorial

Gottlieb: FDA Will Streamline Drug Safety Evaluations

The FDA will soon standardize the way it handles data on the safety and effectiveness of drugs in an effort to reduce inconsistencies in the drug review process. [STAT News] Editorial

NEW 2018 National Cancer Research Institute (NCRI) Cancer Conference
November 4-6, 2018
Glasgow, United Kingdom

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

NEW Research Fellow – Neuropsychiatric Immunology (Cardiff University)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Faculty Position – Aging and the Immune System (Mayo Clinic)

Postdoctoral Position – Autoimmunity (Medical University of South Carolina)

Postdoctoral Fellow – Cancer Innate Immunity (Johnson & Johnson Pharmaceutical Research & Development)

Postdoctoral Scholar – Tumor Immunology and Immunotherapy (Northwestern University Feinberg School of Medicine)

Postdoctoral Position – DNA Damage Response and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Fellow – Immunotherapy (California Institute for Biomedical Research)

Postdoctoral Fellowship Position – Innate Immunity and Neurodegeneration (The Mount Sinai Health System)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Postdoctoral Fellow – Immunoengineering for Muscle Regeneration (Duke University)

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