Volume 4.08 | Mar 1

Human Immunology News 4.08 March 1, 2016
Human Immunology News
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Cancer Metastasis: It All Depends on the Patient’s Immune Response
Investigators analyzed tumors from 838 patients with colorectal cancer, in order to identify markers for their metastatic potential. The genomic characteristics of the cancer cells seem to have little relevance. Conversely, lymphatic vascularization around the tumor and the intensity of the patient’s immune response appear to be crucial, and might be used as markers to predict the progression of the disease. [Press release from Inserm discussing online publication in Science Translational Medicine] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Glycolytic Enzyme PKM2 Bridges Metabolic and Inflammatory Dysfunction in Coronary Artery Disease
Investigators report that in monocytes and macrophages of patients with atherosclerotic coronary artery disease, overutilization of glucose promotes excessive and prolonged production of the cytokines IL-6 and IL-1β, driving systemic and tissue inflammation. [J Exp Med] Abstract | Press Release

Platelet-Derived Microparticles Inhibit IL-17 Production by Regulatory T Cells through P-Selectin
Researchers investigated whether platelet-derived microparticles (PMPs) have the ability to affect regulatory T cell (Treg) plasticity. PMPs were co-cultured with healthy donor peripheral blood-derived Treg that were stimulated with anti-CD3/CD28 monoclonal antibodies in the presence of IL-2, IL-15 and IL-1β. [Blood] Abstract

PD-1 Blockade Boosts Radiofrequency Ablation–Elicited Adaptive Immune Responses against Tumor
Scientists investigated immune-suppressive mechanisms limiting the efficacy of radiofrequency ablation (RFA). They found that RFA treatment of liver metastases increased not only T-cell infiltration, but also PD-L1 expression in primary human colorectal tumors. [Clin Cancer Res] Abstract | Press Release

Matrix Metalloproteinase-10 Is a Target of T and B Cell Responses That Correlate with Synovial Pathology in Patients with Antibiotic-Refractory Lyme Arthritis
Researchers identified an immunogenic HLA-DR-presented peptide derived from the source protein matrix metalloproteinase-10 (MMP-10) from the synovium of a patient with antibiotic-refractory arthritis. After priming of the immune response to MMP-10 in early infection, a subset of patients with antibiotic-responsive or antibiotic-refractory arthritis had MMP-10 autoantibodies, but only patients with antibiotic-refractory arthritis had both T and B cell responses to the protein. [J Autoimmun] Abstract

Human Naïve Regulatory T-Cells Feature High Steady-State Turnover and Are Maintained by IL-7
The authors found that in adults thymectomized early in infancy the naïve-regulatory T-cell pool is remarkably well preserved, in contrast to conventional naïve CD4 T-cells. [Oncotarget] Full Article

Regulatory T Cells Inhibit CD34+ Cell Differentiation into NK Cells by Blocking Their Proliferation
Investigators explored whether regulatory T cell (Treg) therapy impacted natural killer (NK) cell differentiation. Using an in vitro model of hematopoietic stem cell differentiation into NK cells, they found that activated Tregs led to a 90% reduction in NK cell numbers when added at the time of commitment to the NK cell lineage. [Sci Rep] Full Article

Artificial Antigen Presenting Cells Expressing HLA Class II Molecules as an Effective Tool for Amplifying Human Specific Memory CD4+ T Cells
Scientists constructed stable artificial antigen presenting cells (AAPCs) derived from mouse fibroblasts. They showed that AAPCs were able to take up and process whole Ag proteins, and present epitopes to specific T cells. [Immunol Cell Biol] Abstract

Comparative Analysis of Protocols to Induce Human CD4+Foxp3+ Regulatory T Cells by Combinations of IL-2, TGF-Beta, Retinoic Acid, Rapamycin and Butyrate
Investigators comprehensively compared different established and defined novel protocols of human induced regulatory T cell (iTreg) generation using TGF-β in combination with other compounds. They found that human iTregs expressed several Treg signature molecules, such as Foxp3, CTLA-4 and EOS, while exhibiting low expression of the cytokines interferon-γ, IL-10 and IL-17. [PLoS One] Full Article

Glioblastoma-Infiltrated Innate Immune Cells Resemble M0 Macrophage Phenotype
Researchers performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of glioblastoma-associated myeloid cells with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. [JCI Insight] Full Article | Press Release

Autoimmune Response to Transthyretin in Juvenile Idiopathic Arthritis
Using biochemical and proteomic approaches, the authors identified the molecular chaperone transthyretin (TTR) as an antigenic target for B and T cell immune responses. Three cryptic, HLA-DR1–restricted TTR peptides, which induced CD4+ T cell expansion and IFN-γ and TNF-α production in three out of 17 analyzed patients, were also identified. [JCI Insight] Full Article | Press Release

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Memory T Cells in Organ Transplantation: Progress and Challenges
Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. [Nat Rev Nephrol] Abstract

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Late-Breaking Research Shows Promise for Patients with Primary Progressive Multiple Sclerosis
In a randomized, double-blind, placebo-controlled Phase III study, ocrelizumab significantly reduced disease activity in patients with primary progressive multiple sclerosis. [Press release from Americas Committee for Treatment and Research in Multiple Scleroses (ACTRIMS; Newswise, Inc.) discussing research presented at the 2016 ACTRIMS Forum, New Orleans] Press Release

Compugen Presents Results for CGEN-15029 Immuno-Oncology Therapeutic Program
Compugen USA, Inc. presented results for CGEN-15029, the lead internal program in the company’s immuno-oncology therapeutics pipeline. [Press release from Compugen USA, Inc. discussing research presented at Emerging Approaches to Cancer Immunotherapy, New York] Press Release

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CAR Trials Drive Leukemia and Lymphoma Treatment in New Direction
Researchers at UC San Diego Moores Cancer Center have launched three clinical trials to test the safety and efficacy of a novel cellular-immunotherapy that uses modified T cells – one of the immune system’s primary weapons – to treat three different types of blood cancer that often defy existing therapies. [UC San Diego Health] Press Release

Lilly Receives Positive CHMP Opinion for Ixekizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis
Eli Lilly and Company announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion for ixekizumab for the treatment of moderate-to-severe plaque psoriasis in adults in the European Union who are candidates for systemic therapy. [Eli Lilly and Company] Press Release

SELLAS Life Sciences Announces FDA Orphan Drug Designation for WT1 Cancer Vaccine in Patients with Malignant Pleural Mesothelioma
SELLAS Life Sciences Group announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation for the company’s WT1 cancer vaccine for the treatment of patients with malignant pleural mesothelioma. [SELLAS Life Sciences Group] Press Release

Prostate Cancer Vaccine Trial Seeks Volunteers
In an initial study led by Professor Freddie Hamdy and Professor Jim Catto, researchers will vaccinate 48 men with low or intermediate risk prostate cancer to document the safety of the new vaccine and measure how well the immune system to responds to it. [Oxford University] Press Release

OncBioMune Continuing Phase I Trial, While Initiating Phase II Trial of ProscaVax for Prostate Cancer
OncBioMune Pharmaceuticals, Inc. reported positive results from its Phase I clinical trial of ProscaVax, the company’s novel cancer vaccine for prostate cancer. [OncBioMune Pharmaceuticals, Inc.] Press Release
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