Human Immunology News Volume 8.03 | Jan 28 2020

TOP STORY

White Blood Cell and Cell-Free DNA Analyses for Detection of Residual Disease in Gastric Cancer

Researchers identified circulating tumor-derived DNA alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. They applied this approach to analyze samples from patients in the CRITICS trial, a Phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Human Liver Memory CD8⁺ T Cells Use Autophagy for Tissue Residence

By performing ex vivo staining of freshly isolated cells from human liver tissue, the authors found that an increased rate of basal autophagy was a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8⁺ T cells. CD8⁺ T cells with increased autophagy were those best able to proliferate and mediate cytotoxicity and cytokine production. Conversely, blocking autophagy induction resulted in the accumulation of depolarized mitochondria, a feature of exhausted T cells. [Cell Rep] Full Article | Graphical Abstract

DuoBody-CD3xCD20 Induces Potent T-Cell-Mediated Killing of Malignant B Cells in Preclinical Models and Provides Opportunities for Subcutaneous Dosing

T-cell activation and T-cell-mediated cytotoxicity were measured by flow cytometry following co-culture with tumor cells. Anti-tumor activity of DuoBody-CD3xCD20 was assessed in humanized mouse models in vivo. Non-clinical safety studies were performed in cynomolgus monkeys. [EBioMedicine] Full Article

Development of a Protein-Based System for Transient Epigenetic Repression of Immune Checkpoint Molecule and Enhancement of Antitumor Activity of Natural Killer Cells

A protein-based genome modulator system is composed of a transcription activator-like effector, DNA methyltransferase and a newly identified potent cell-penetrating peptide with nuclear-trafficking property named NTP. Transcription activator-like effector was designed to target the promoter region of the programmed cell death-1 gene. After culturing human NK cells in the presence of NTP-GM protein, investigators examined endogenous PD-1 expression and anti-tumor activity of the treated cells. [Br J Cancer] Abstract

Combined Anti-CD20 and mTOR Inhibition with Factor VIII for Immune Tolerance Induction in Hemophilia a Patients with Refractory Inhibitors

Two refractory hemophilia A inhibitor patients were treated with rituximab, rapamycin and factor VIII (FVIII) immune tolerance induction. Their clinical course, anti-FVIII immunoglobulins, cytokines, and select lymphocytes were followed. One patient achieved complete and the other partial FVIII tolerance; both had marked annualized bleeding rate improvement. [J Thromb Haemost] Abstract

Unique Natural Killer Cell Subpopulations Are Associated with Exacerbation Risk in Chronic Obstructive Pulmonary Disease

Using high-dimensional flow cytometry, scientists phenotyped peripheral blood NK cells from never smokers, smokers, and COPD patients and employed a non-supervised clustering algorithm to define and detect changes in NK cell populations. They identified greater than 1,000 unique NK cell subpopulations across patient groups and describe 13 altered NK populations in patients who experienced prior exacerbations. [Sci Rep] Full Article

The Role of Human Leukocyte Antigen Class I on Patient Survival in Gastrointestinal Cancers: A Systematic Review and Meta- Analysis

Researchers performed a meta-analysis to determine the role of classical human leukocyte antigen class I (HLA)-I in predicting survival of patients. The relationship between HLA- I and some clinicopathological factors was evaluated. Published studies investigated HLA-I expression effect on gastrointestinal cancers were evaluated to determine association between HLA-I and overall survival and recurrence-free survival in patients. [Sci Rep] Full Article

Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients

The authors evaluated the impact of hepatitis C virus (HCV) on the T-cell-mediated immune response to tuberculosis (TB) in coinfected patients. 64 patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4⁺ T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. [Viruses] Full Article

IL-36α Contributes to Enhanced T Helper 17 Type Responses in Allergic Rhinitis

Twenty-one patients with allergic rhinitis (AR) and 20 healthy controls were enrolled. The expression of serum protein and mRNA of IL-36 family cytokines between AR and control group were detected and compared. Human peripheral blood mononuclear cells were purified and stimulated by IL-36 cytokines. [Cytokine] Abstract

TLR3 Activation Modulates Immunomodulatory Properties of Human Periodontal Ligament Cells

Human periodontal ligament cells (hPDL) cells were treated with various doses of poly I:C, a toll-like receptors (TLR3) activator. The expression of interferon-gamma, indoleamine 2,3 dioxygenase and human leukocyte antigen G was determined. Chemical inhibitors and small interfering RNA were used to confirm the role of TLR3. Co-culture with human peripheral blood mononuclear cells with poly I:C-activated hPDL cells was performed. [J Periodontol] Abstract

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B Cells, Plasma Cells and Antibody Repertoires in the Tumor Microenvironment

Investigators summarize the current knowledge of the roles of B cells and antibodies in the tumor micro-environment. Moreover, they discuss the potential of using immunoglobulin repertoires as a source of tumor-specific receptors for immunotherapy or as biomarkers to predict the efficacy of immunotherapeutic interventions. [Nat Rev Immunol] Abstract

Siglecs as Immune Cell Checkpoints in Disease

Because of sialic acid-binding immunoglobulin-type lectins (Siglecs) restricted cell type expression and roles as checkpoints in immune cell responses in human diseases such as cancer, asthma, allergy, neurodegeneration, and autoimmune diseases they have gained attention as targets for therapeutic interventions. The authors describe the Siglec family, its roles in regulation of immune cell signaling, current efforts to define its roles in disease processes, and approaches to target Siglecs for treatment of human disease. [Annu Rev Immunol] Abstract

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

Ervaxx and Cardiff University Enter Collaboration to Develop Novel T-Cell and T-Cell Receptor-Based Immunotherapeutics Targeting Dark Antigens™

Ervaxx™ has entered a licensing and research collaboration with a leading T-cell immunology group at Cardiff University. The new collaboration will support a multi-year research program with Prof. Andrew Sewell’s T-cell modulation group at Cardiff University focusing on the discovery and characterization of T-cells and T-cell receptor reactive to cancer-specific antigens and ligands, including Ervaxx’ proprietary Dark Antigens™. [Ervaxx™] Press Release

Aphios Granted US Patent for Combination HIV Latency Nanotherapeutic Towards an HIV Cure

Aphios Corporation announced that it was issued US Patent No. 10,493,030 for the treatment of HIV latency towards an HIV cure. [Aphios Corporation] Press Release

Feds Fund Innovative Health Research Happening at DAL, NSHA and IWK

Dalhousie University is home to four of the newest recipients of funding from the Government of Canada for their innovative health research. The $1,159,527 in funding is provided by the Canadian Institutes of Health Research Project Grants, which help researchers gather the kind of information they need to make real improvements to clinical practice, health service delivery, and public health policy. [Dalhousie University] Press Release

Top Harvard Chemist Charged with Lying about Ties to Chinese Government Program

The head of Harvard University’s chemistry department was charged with attempting to conceal his involvement in a Chinese government program to bring scientists to China, an escalation of a crackdown by US authorities on what they perceive as a campaign to steal ideas born in American universities and medical centers. [STAT News] Editorial

Iranian Students Denied Entry to US

Despite having valid visas to attend universities, more than a dozen would-be graduate students have been detained at the airport and sent back to Iran in recent months. [The Scientist] Editorial

Brazil’s Pick of a Creationist to Lead Its Higher Education Agency Rattles Scientists

The appointment of a creationism advocate to lead the agency that oversees Brazil’s graduate study programs has scientists there concerned-yet again-about the encroachment of religion on science and education policy. President Jair Bolsonaro’s administration on Saturday January 25^th named Benedito Guimarães Aguiar Neto to head the agency, known as CAPES, who previously served as the rector for a private religious school which advocates the teaching and study of intelligent design. [ScienceInsider] Editorial

NEW Keystone Symposium: T Cell Memory
March 1-5, 2020
Banff, Alberta, Canada

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

NEW Professorship – Antimicrobial Resistance (University Hospital of Cologne)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Bioengineering (STEMCELL Technologies Inc.)

Research Scientist – Immuno-Oncology (Ervaxx)

Postdoctoral Position – Tumor Immunology (University Hospital Carl Gustav Carus Dresden)

Chief – Division of Immunology (Boston Children’s Hospital)

Research Assistant Professor – Immunology (The University of Chicago)

Postdoctoral Fellowship – Breast Cancer Immunology and Immunotherapy (The University of Texas Southwestern Medical Center)

Postdoctoral Fellow – Immune Defense and HIV (Massachusetts General Hospital)

Postdoctoral Position – Blood Cancer Immunology (University Children’s Hospital Basel)

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