Immune Regulation News Volume 4.39 | Oct 12 2012

Melanomas Resist T-Cell Therapy through Inflammation-Induced Reversible Dedifferentiation
Researchers report that melanomas acquire adoptive cell transfer therapy resistance through an inflammation-induced reversible loss of melanocytic antigens. They identified the proinflammatory cytokine tumor necrosis factor (TNF)-α as a crucial factor that directly caused reversible dedifferentiation of mouse and human melanoma cells. Tumor cells exposed to TNF-α were poorly recognized by T cells specific for melanocytic antigens, whereas recognition by T cells specific for non-melanocytic antigens was unaffected or even increased. [Nature] Abstract | Press Release

CSK Regulatory Polymorphism Is Associated with Systemic Lupus Erythematosus and Influences B-Cell Signaling and Activation
Investigators identified an association of CSK with systemic lupus erythematosus and refined its location to the intronic polymorphism rs34933034. The risk allele at this SNP is associated with increased CSK expression and augments inhibitory phosphorylation of Lyn. In carriers of the risk allele, there is increased B-cell receptor-mediated activation of mature B cells, as well as higher concentrations of plasma immunoglobulin M, relative to individuals with the non-risk haplotype. [Nat Genet] Abstract

The Transcription Factor GATA-3 Controls Cell Fate and Maintenance of Type 2 Innate Lymphoid Cells
Data demonstrated that GATA-3 is essential for type 2 innate lymphoid cell (ILC2) fate decisions and revealed similarities between the transcriptional programs controlling ILC and T helper cell fates. [Immunity] Abstract

The Transcription Factors Thpok and LRF Are Necessary and Partly Redundant for T Helper Cell Differentiation
Although transcription factors have been identified that direct T helper (Th) cells into specific effector fates, whether a “master” regulator controls the developmental program common to all Th cells remains unclear. Here, researchers showed that the two transcription factors Thpok and LRF share this function. [Immunity] Abstract

Interleukin 7 (IL-7) Selectively Promotes Mouse and Human IL-17-Producing γδ Cells
Murine IL-17-producing CD27⁻ γδ T cells and thymocytes were shown to be rapidly and substantially expanded by IL-7 in vitro and in vivo. IL-7 promoted strong responses of IL-17-producing γδ cells to TCR agonists, thus reemphasizing the cells’ adaptive and innate potentials. [Proc Natl Acad Sci USA] Abstract | Full Article

Dendritic Cells Sequester Antigenic Epitopes for Prolonged Periods in the Absence of Antigen-Encoding Genetic Information
Scientists demonstrated that epitopes, or epitope precursors, of a model antigen persist in a host for prolonged periods, well beyond the time at which the intact antigen has disappeared, and in the complete absence of genetic information encoding it. Dendritic cells are shown to be the site of this epitope sequestration in vivo, as well as in cultures in vitro. [Proc Natl Acad Sci USA] Abstract | Full Article

Bcl6 Controls the Th2 Inflammatory Activity of Regulatory T Cells by Repressing Gata3 Function
Bcl6-deficient (Bcl6^−/−) mice develop a spontaneous and severe Th2-type inflammatory disease, thus warranting assessment of Bcl6 in regulatory T cell (Treg) function. Bcl6^−/− Tregs were competent at suppressing T cell proliferation in vitro and Th1-type colitogenic T cell responses in vivo. In contrast, Bcl6^−/− Tregs strongly exacerbated lung inflammation in a model of allergic airway disease and promoted higher Th2 responses, including systemic upregulation of microRNA-21. [J Immunol] Abstract

Regression of Human Prostate Cancer Xenografts in Mice by MT112/BAY2010112, a Novel PSMA/CD3-Bispecific BiTE Antibody Crossreactive with Non-Human Primate Antigens
For treatment of patients with prostate cancer, researchers developed a novel T cell-engaging (BiTE) antibody designated MT112 or BAY2010112 that is bispecific for prostate-specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex. MT112/BAY2010112 induced target cell-dependent activation and cytokine release of T cells, and efficiently redirected T cells for lysis of target cells. [Mol Cancer Ther] Abstract

Syntaxin 11 Is Required for NK and CD8+ T-Cell Cytotoxicity and Neutrophil Degranulation
Since Syntaxin 11 (Stx11) mutations are causally associated with a familial hemophagocytic lymphohistiocytosis, researchers wanted to clarify whether STX11 is functionally important for key immune cell populations. They found that STX11 selectively controls lymphocyte cytotoxicity in NK and activated CD8⁺ T cells and degranulation in neutrophils. [Eur J Immunol] Abstract

CD4 Helper T Cells, CD8 Cytotoxic T Cells, and FOXP3⁺ Regulatory T Cells with Respect to Lethal Prostate Cancer
Researchers concluded that men with greater numbers of CD4⁺ regulatory T cells in their prostate tumor environment have an increased risk of dying of prostate cancer. [Mod Pathol] Abstract

Treg Cells in Pancreatic Lymph Nodes: The Possible Role in Diabetogenesis and β Cell Regeneration in a Type 1 Diabetes Model
The authors investigated the role of T regulatory (Treg) cells in the mechanisms mediating the restoration of euglycemia in the antea-diabetic non-obese diabetic (NOD) model. The data demonstrated that the numbers of Treg cells were decreased in unmanipulated NOD mice, with the most profound deficiency detected in the pancreatic lymph nodes. [Cell Mol Immunol] Abstract | Press Release

B Cells and Antibodies in Multiple Sclerosis Pathogenesis and Therapy
This review summarizes key features of B-cell biology, the role of B cells and antibodies in CNS inflammation, and current attempts to identify the targets of pathogenic antibodies in multiple sclerosis. [Nat Rev Neurol] Abstract

MedImmune Joins Forces with Leading Cancer Organizations to Advance Novel Immunotherapy Research
The Cancer Research Institute, the Ludwig Institute for Cancer Research and MedImmune announced that they have signed a collaboration agreement to advance the research of immunotherapy in cancer. Specifically, the research will focus on clinical trials to test novel combinations of immunotherapies, including three investigational monoclonal antibodies from MedImmune’s pipeline. [MedImmune, LLC] Press Release

NewLink Genetics Launches Phase III Clinical Trial of algenpantucel-L Immunotherapy in Patients with Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
NewLink Genetics Corporation announced the launch of an open-label, randomized, multi-institutional Phase III study in patients with borderline resectable or locally advanced unresectable pancreatic cancer. The projected enrollment will be 280 subjects and patients will be randomized (1:1) to receive standard of care FOLFIRINOX plus or minus algenpantucel-L immunotherapy. [NewLink Genetics Corporation] Press Release

Immunovative, Inc. Announces Issuance of U.S. Patent on Key Scientific Breakthrough
Immunovative, Inc. announced that Immunovative Therapies, Ltd. has been granted a U.S. Patent entitled “METHOD FOR ALLOGENEIC CELL THERAPY,” under Patent No. 8,273,377. This patent covers the proprietary method that utilizes immune cells from a normal donor to elicit an anti-tumor mechanism that mimics the Graft vs. Tumor effect of non-myeloablative allogeneic stem cell transplants without the toxicity of Graft vs. Host Disease. [Immunovative, Inc.] Press Release

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NEW Frontiers in Cancer Science 2012
November 5-8, 2012
Singapore, Singapore

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