Human Immunology News Volume 1.05 | Apr 16 2013

PUBLICATIONS (Ranked by impact factor of the journal)

Ex Vivo Expansion of Highly Cytotoxic Human NK Cells by Cocultivation with Irradiated Tumor Cells for Adoptive Immunotherapy
Natural killer (NK) cells can kill a wide range of tumor cells by patterned recognition of target ligands. The authors hypothesized that tumor targets sensitive to NK lysis would drive vigorous expansion of NK cells from human peripheral blood mononuclear cells. This study provides the basis for developing a novel ex vivo expansion process. [Cancer Res] Abstract

Sulfasalazine and Thalidomide Inhibit Extracellular Trap Formation by Human Neutrophils
Using neutrophils isolated from human donors, the authors investigated the effects of various drugs on neutrophil extracellular trap formation  (NETosis). Through immunofluorescence and assays measuring extruded extracellular trap DNA, they demonstrated that sulfasalazine, thalidomide, and to a lesser extent DMSO, inhibit NETosis of human neutrophils. In contrast, cyclosporine, tacrolimus, tetracycline, colchicine, hydroxychloroquine, cromolyn, or dapsone had no significant effect on NETosis. [J Invest Dermatol] Abstract

IL-31 Is Produced by the Malignant T Cell Population in Cutaneous T-Cell Lymphoma and Its Expression Correlates with Pruritus
Patients with Mycosis Fungoides and Sézary syndrome, the two most common types of Cutaneous T-cell lymphomas (CTCL), may suffer from intense pruritus, which can cause significant morbidity and decreased quality of life. IL-31, a cytokine produced primarily by CD4 T cells, has been shown to be highly associated with pruritus in atopic dermatitis, allergic contact dermatitis and prurigo nodularis. Researchers therefore sought to investigate the relationship of IL-31 to pruritus in CTCL. [J Invest Dermatol] Abstract

Vitamin D Enhances Glucocorticoid Action in Human Monocytes: Involvement of Granulocyte-Macrophage Colony-Stimulating Factor and Mediator Complex Subunit 14
Scientists demonstrated that Vitamin D (VitD) enhanced glucocorticoid (GC) responses in human peripheral blood mononuclear cells as it stimulated GC induction of mitogen-activated protein kinase phosphatase-1 and enhanced GC inhibition of LPS-induced IL-6. These VitD effects were abolished in purified CD14+ and CD14- cells, but were recovered in CD14+ cells co-cultured with CD14- cells separated by tissue culture inserts. [J Biol Chem] Abstract

Erythropoietin Administration Suppresses Human Monocyte Function In Vitro and during Therapy-Induced Anemia in Hepatitis C Virus Patients
Researchers examined the immunological effects of erythropoietin (EPO) on human monocytes. They showed that human monocytes express EPO receptor mRNA, and are responsive to EPO in cell culture. In vitro exposure of peripheral blood mononuclear cells from individuals to EPO and the TLR4 ligand LPS showed a significant reduction of monocytes producing IL-6 and TNF, while the frequencies of IL-12p40, IL-10, MIP-1β and IL-8-producing cells did not change upon incubation with EPO. [Antiviral Res] Abstract

Preoperative Irradiation for the Prevention of Heterotopic Ossification Induces Local Inflammation in Humans
As inflammatory processes are suggested to be involved in the pathogenesis of heterotopic ossification (HO), researchers hypothesized that the preoperative irradiation impacts local immune components. Therefore, they quantified immune cell populations and cytokines in hematomas resulting from the transection of the femur in two groups of patients receiving total hip arthroplasty: patients irradiated preoperatively in the hip region (7 Gy) in order to prevent HO and patients who were not irradiated but were postoperatively treated with non-steroidal anti-inflammatory drugs. [Bone] Abstract

Natural IgG Autoantibodies Are Abundant and Ubiquitous in Human Sera, and Their Number Is Influenced By Age, Gender, and Disease
Immune-response profiling of human serum from 166 individuals via human protein microarrays demonstrated that IgG autoantibodies are abundant in all human serum, usually numbering in the thousands. These IgG autoantibodies bind to human antigens from organs and tissues all over the body and their serum diversity is strongly influenced by age, gender, and the presence of specific diseases. [PLoS One]
Full Article | Press Release

Elevated Numbers of Regulatory T Cells, Central Memory T Cells and Class-Switched B Cells in Cerebrospinal Fluid of Patients with Anti-Hu Antibody Associated Paraneoplastic Neurological Syndromes
Multi-parametric flow cytometry was used to study lymphocyte subsets and dendritic cells in paired blood and cerebrospinal fluid samples from 11 newly diagnosed patients with progressive anti-Hu antibody associated paraneoplastic neurological syndromes, nine patients with other inflammatory neurologic disorders, and 12 patients with other non-inflammatory neurologic disorders. [J Neuroimmunol] Abstract

Maternal and Infant Infections Stimulate a Rapid Leukocyte Response in Breastmilk
Breastmilk protects infants against infections; however, specific responses of breastmilk immune factors to different infections of either the mother or the infant are not well understood. Researchers examined the baseline range of breastmilk leukocytes and immunomodulatory biomolecules in healthy mother/infant dyads and how they are influenced by infections of the dyad. [Clin Transl Immunol] Full Article

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The Aging Hematopoietic Stem Cell Compartment
The authors summarize the phenotypes of aging hematopoietic stem cells (HSCs) and discuss how the cell-intrinsic and cell-extrinsic mechanisms of HSC aging might promote immunosenescence. Stem cell aging has long been considered to be irreversible. However, recent findings indicate that several molecular pathways could be targeted to rejuvenate HSCs and thus to reverse some aspects of immunosenescence. [Nat Rev Immunol] Abstract

Molecular Mechanisms of Natural Killer Cell Activation in Response to Cellular Stress
This review provides a brief introduction to natural killer (NK) cells and the relevant receptors and ligands involved in direct responses to cellular stress. This is followed by an in-depth discussion surrounding the various intrinsic responses to stress that can naturally engage NK cells, and how therapeutic agents may induce specific activation of NK cells and other innate immune cells by activating cellular responses to stress. [Cell Death Differ] Abstract

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

Engineered Antibody Demonstrated Safety, Efficacy in Wide Range of Advanced Tumors
The engineered antibody MPDL3280A, which targets a protein called programmed death-ligand 1, was safe and effective for several cancers, according to phase I study results. [Press release from the American Association for Cancer Research (AACR) discussing research presented at the AACR Annual Meeting 2013, Washington.] Press Release

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Immune Therapy from Austria Receives Orphan Drug Designation from European Medicines Agency
The European Medicines Agency recently awarded the Austrian biotech company Activartis an Orphan Drug Designation for its innovative Cancer Immune Therapy AV0113. The Orphan Drug Designation applies specifically to the use of AV0113 for the treatment of glioma, a type of brain tumor, which afflicts around one in 10,000 people in the EU. [Activartis Biotech GmbH] Press Release

Immunotherapies Against Cancer: German Cancer Research Center to Broaden Strategic Alliance with Bayer HealthCare
The German Cancer Research Center and Bayer HealthCare will extend their successful strategic research alliance in search of novel cancer therapeutics by focusing their activities also on the field of immunotherapy. [German Cancer Research Center] Press Release

T Cell Biology Pioneer Allison Wins First AACR Honor for Cancer Immunology
The scientist whose discoveries led to the first drug approved for metastatic melanoma by “treating the immune system, not the cancer,” also is the first to receive the AACR-CRI Lloyd J. Old Award in Cancer Immunology. James Allison, Ph.D., professor and chair of The University of Texas MD Anderson Cancer Center Department of Immunology, was honored at the AACR Annual Meeting 2013 in Washington, D.C. [The University of Texas MD Anderson Cancer Center] Press Release

Pharmacyclics Triggers Fourth Milestone Payment for Enrollment of 5th Patient in Frontline Phase III CLL Study
Pharmacyclics, Inc. announced that the Phase III clinical trial (RESONATE™-2), a monotherapy trial using ibrutinib versus chlorambucil in elderly patients with newly diagnosed chronic lymphocytic leukemia (CLL) / small lymphocyctic lymphoma has enrolled its fifth patient. The enrollment of the fifth patient has subsequently triggered a fourth $50 million milestone payment obligation from Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, worldwide collaborator on ibrutinib in oncology. [Pharmacyclics, Inc.] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

Scientist – Immunology (Crucell Holland B.V.)

Physician/Scientist – Tumor Immunotherapy (Stanford University School of Medicine)

Postdoctoral Fellow – Cancer Immunology (Dana-Farber Cancer Institute / Harvard Medical School)

Research Fellow – Readership in Immunology (University of Edinburgh)

Postdoctoral Position – Type 1 Diabetes and Systemic Lupus Erythematosus (University of Florida)

Postdoctoral Positions – Medical Science (University of Oslo)

Senior Director – Department of Immunology (Genentech, Inc.)

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