Human Immunology News Volume 3.14 | Apr 14 2015

Extracellular Poly(ADP-Ribose) Is a Pro-Inflammatory Signal for Macrophages
Researchers found that poly(ADP-ribose) (PAR) activated cytokine release in human and mouse macrophages, a hallmark of innate immune activation, and determined structure-activity relationships. PAR was rapidly internalized by murine macrophages, while the monomer, ADP-ribose, was not. [Chem Biol]
Abstract | Graphical Abstract

T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01⁺ Cells
The authors describe a human self-peptide that is a homolog of a highly immunogenic EBV T cell epitope presented by HLA-B*18:01. A significant proportion of CD8⁺ T cells raised from some healthy individuals against this EBV epitope cross-reacted with the self-peptide. [J Immunol] Abstract

Regulatory T Cells-Derived IL-35 Promotes the Growth of Adult Acute Myeloid Leukemia Blasts
Scientists found that IL-35 was expressed highly in peripheral blood plasma of adult acute myeloid leukemia (AML) patients and significantly correlated with the clinical stages of malignancy. CD4⁺CD25⁺ regulatory T cells-derived from adult AML patients produced IL-35 in a stimulation-dependent manner. [Int J Cancer] Abstract

IL-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus Infected Macrophages
Investigators report that peripheral blood natural killer cells from human cytomegalovirus (HCMV) seropositive donors showed an enhanced activity towards HCMV infected autologous macrophages. [J Virol] Abstract

B7H6-Specific Chimeric Antigen Receptors Lead to Tumor Elimination and Host Anti-Tumor Immunity
B7H6, a ligand for the NK cell activating receptor NKp30, was targeted to create a chimeric antigen receptor (CAR) which targets multiple tumor types. B7H6-specific CAR T cells have robust cellular cytotoxicity and IFN‑γ secretion when co-cultured with B7H6⁺ tumor cells, and they exhibit little self-reactivity to immature dendritic cells or pro-inflammatory monocytes. [Gene Ther] Abstract

Engineering Monocyte-Derived Dendritic Cells to Secrete Interferon-α Enhances Their Ability to Promote Adaptive and Innate Anti-Tumor Immune Effector Functions
Scientists hypothesized that engineering easily generated human monocyte-derived mature dendritic cells to secrete interferon-α using mRNA electroporation enhances their ability to promote adaptive and innate anti-tumor immunity. [Cancer Immunol Immunother] Abstract

T Lymphocyte Density and Distribution in Human Colorectal Mucosa, and Inefficiency of Current Cell Isolation Protocols
The authors identified and quantified in human distal colorectal tissue absolute mucosal CD3⁺ lymphocytes, including CD4⁺ and CD8⁺ subsets, by direct visualization using immunohistochemistry, immunofluorescence, and an automated counting protocol. [PLoS One] Full Article

Functional Characterization of Human T Cell Hyporesponsiveness Induced by CTLA4-Ig
Scientists established a model to study the effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig showed that co-stimulation blockade during TCR activation did not affect NFAT signaling but resulted in decreased activation of NF-κB and AP-1 transcription factors followed by a profound decrease in proliferation and cytokine production. [PLoS One] Full Article

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Neoantigens in Cancer Immunotherapy
Recent technological innovations have made it possible to dissect the immune response to patient-specific neoantigens that arise as a consequence of tumor-specific mutations, and emerging data suggest that recognition of such neoantigens is a major factor in the activity of clinical immunotherapies. [Science]
Abstract | Press Release

The Promise of γδ T Cells and the γδ T Cell Receptor for Cancer Immunotherapy
Ligand recognition by the γδ T cell receptor often requires accessory/co-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. The authors present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment. [Cell Mol Immunol] Abstract

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IOmet Pharma Demonstrates Superior In Vivo PK/PD Properties in Pre-Clinical IDO1, TDO and Dual IDO1/TDO Cancer Immunotherapy Programs
IOmet Pharma will present data demonstrating superior properties of its novel, pre-clinical IDO1, TDO and IDO1/TDO Dual Inhibitor programs. [Press release from IOmet Pharma discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting, San Diego] Press Release

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Roche Aims for 11 Late-Stage Trials in Cancer Immunotherapy Drug This Year
Roche aims to have an immunotherapy cancer drug in 11 late-stage trials by the end of the year, the Swiss drugmaker’s head of medical affairs for oncology, Nico Andre, said at a conference. [F. Hoffmann-La Roche Ltd. (Thomson Reuters)] Press Release

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