Immune Regulation News Volume 7.30 | Aug 14 2015

RORC1 Regulates Tumor-Promoting “Emergency” Granulo-Monocytopoiesis
Scientists identified subsets of myeloid-derived suppressor cells and tumor-associated macrophages based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrated myelopoiesis by suppressing negative and promoting positive regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage. [Cancer Cell] Full Article | Graphical Abstract

Inhibition of Dectin-1 Signaling Ameliorates Colitis by Inducing Lactobacillus-Mediated Regulatory T Cell Expansion in the Intestine
Researchers found that Dectin-1-deficient mice were refractory to both dextran sodium sulfate- and CD45RB^highCD4⁺ T cell-induced colitis, and that this resistance was associated with an increase in regulatory T cells. [Cell Host Microbe] Abstract | Graphical Abstract

IL-21-Mediated Non-Canonical Pathway for IL-1β Production in Conventional Dendritic Cells
Scientists showed that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 did not induce Il1b expression in CD4⁺ T cells, with differential histone marks present in these cells versus cDCs. [Nat Commun] Full Article

The Amino Acid Sensor GCN2 Inhibits Inflammatory Responses to Apoptotic Cells Promoting Tolerance and Suppressing Systemic Autoimmunity
The metabolic-stress sensing protein kinase GCN2 is a primary downstream effector of indoleamine 2,3 dioxygenase 1 (IDO1); thus, investigators tested its role in apoptotic cell-driven immune suppression. In vitro, expression of IDO1 in macrophages significantly enhanced apoptotic cell-driven IL-10 and suppressed IL-12 production in a GCN2-dependent mechanism. [Proc Natl Acad Sci USA] Abstract

Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy
Investigators report that an alternatively activated (M2) subpopulation of tumor-associated macrophages (MRC1⁺TIE2^HiCXCR4^Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. [Cancer Res] Abstract | Press Release

Intestinal Monocyte-Derived Macrophages Control Commensal-Specific Th17 Responses
Researchers examined the roles of mucosal dendritic cells (DCs) and macrophages (Mfs) in Th17 induction by segmented filamentous bacteria (SFB) in vivo. They showed that Mfs, and not conventional CD103⁺ DCs, are essential for the generation of SFB-specific Th17 responses. [Cell Rep] Full Article | Graphical Abstract

CD11c⁺ Monocyte/Macrophages Promote Chronic Helicobacter hepaticus-Induced Intestinal Inflammation through the Production of IL-23
By combining conditional gene ablation and gene expression profiling, scientists found that interleukin-23 (IL-23) production by CD11c⁺ mononuclear phagocytes was essential to trigger intestinal immunopathology and identified major histocompatibility complex class II positive monocytes and macrophages as the major source of IL-23. [Mucosal Immunol] Full Article

Reciprocal Relationship of T Regulatory Cells and Monocytic Myeloid-Derived Suppressor Cells in LP-BM5 Murine Retrovirus-Induced Immunodeficiency
IL-10-producing FoxP3⁺ T regulatory cells (Tregs) expanded after LP-BM5 infection. Following in vivo adoptive transfer of natural Treg (nTreg) depleted CD4⁺ T-cells, and subsequent LP-BM5 retroviral infection, enriched monocytic myeloid derived suppressor cells from these nTreg-depleted mice displayed altered phenotypic subsets. [J Gen Virol] Abstract

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Johnson & Johnson Innovation Announces Collaboration on Immuno-Oncology Antibody ADC-1013 with Alligator Bioscience
Janssen Biotech, Inc. announced an exclusive, worldwide license agreement with Alligator Bioscience AB for ADC-1013, an immuno-oncology agent currently in Phase I clinical studies. [Janssen Biotech, Inc.] Press Release

Immune Design Announces Phase II Cancer Immunotherapy Trial Collaboration
Immune Design announced it has entered into a clinical trial collaboration with Genentech to evaluate the safety and efficacy of Immune Design’s CMB305 cancer immunotherapy product candidate combined with the investigational cancer immunotherapy atezolizumab in a randomized Phase II trial in patients with soft tissue sarcoma. [Immune Design] Press Release

Vitae Pharmaceuticals Announces Initiation of a Phase I Multiple Ascending Dose Study of VTP-43742 in Autoimmune Disorders
Vitae Pharmaceuticals, Inc. announced that it has initiated a Phase I multiple ascending dose clinical trial of VTP-43742, its wholly owned and first-in-class RORγt inhibitor product candidate for the treatment of autoimmune disorders, including psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis and multiple sclerosis, as well as numerous orphan indications. [Vitae Pharmaceuticals, Inc.] Press Release

Sorrento’s TNK Therapeutics Subsidiary Acquires Multiple Clinical Stage CAR-T Immunotherapy Programs
Sorrento Therapeutics, Inc. announced that its wholly-owned subsidiary, TNK Therapeutics, Inc., has acquired multiple preclinical and clinical stage chimeric antigen receptor (CAR)-T immunotherapy programs as well as underlying CAR-T technology through the acquisition of two privately-held biotechnology companies. [Sorrento Therapeutics, Inc.] Press Release

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