Immune Regulation News Volume 11.04 | Feb 8 2019

TOP STORY

Anti-Tumor Immunity Controlled through mRNA m⁶A Methylation and YTHDF1 in Dendritic Cells

Scientists showed that durable neoantigen-specific immunity was regulated by mRNA N⁶-methyadenosine (m⁶A) methylation through the m⁶A-binding protein YTHDF1 [Nature] Abstract | Editorial

(Ranked by impact factor of the journal)

Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease

In the setting of celiac disease, where exposure to dietary antigen can be controlled, gluten-induced inflammation triggered a profound depletion of naturally occurring Vγ4⁺/Vδ1⁺ intraepithelial lymphocytes with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. [Cell] Abstract | Press Release | Graphical Abstract

An Essential Role for the Zn²⁺ Transporter ZIP7 in B Cell Development

Researchers report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. [Nat Immunol] Abstract

Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity

A Syk-kinase-coupled signaling pathway in dendritic cells was critical for commensal-dependent production of interleukin (IL)-17 and IL-22 by CD4⁺ T cells. The Syk-coupled C-type lectin receptor Mincle detected mucosal-resident commensals in the Peyer’s patches, triggered IL-6 and IL-23p19 expression, and thereby regulated function of intestinal T helper 17- and IL-17-secreting innate lymphoid cells. [Immunity] Full Article | Graphical Abstract

Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade

The authors found that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tumors, this combination compromised anti-tumor immunity in the low tumor burden state in pre-clinical models as well as in melanoma patients. Activated tumor-specific T cells expressed higher amounts of interferon-γ receptor and were more susceptible to apoptosis than naive T cells. [Immunity] Abstract | Graphical Abstract

Modulation of the Sigma-1 Receptor-IRE1 Pathway Is Beneficial in Preclinical Models of Inflammation and Sepsis

Investigators identified the endoplasmic reticulum-resident protein sigma-1 receptor (S1R) as an essential inhibitor of cytokine production in a preclinical model of septic shock. Mice lacking S1R succumbed quickly to hypercytokinemia induced by a sublethal challenge in two models of acute inflammation. [Sci Transl Med] Abstract

Intestinal Non-Canonical NFκB Signaling Shapes the Local and Systemic Immune Response

Scientists showed that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase was highly active in intestinal lymphoid follicles, and was required for M-cell maintenance. [Nat Commun] Full Article

Pharmacological Reactivation of MYC-Dependent Apoptosis Induces Susceptibility to Anti-PD-1 Immunotherapy

Researchers demonstrated the translational potential of an AMPK and BCL-2/BCL-XL co-targeting strategy in ex vivo and in vivo models of MYC-high breast cancer. Metformin combined with navitoclax or venetoclax efficiently inhibited tumor growth, conferred survival benefits and induced tumor infiltration by immune cells. [Nat Commun] Full Article | Press Release

The Mechanistic Study behind Suppression of GvHD while Retaining GvL Activities by Myeloid-Derived Suppressor Cells

Using multiple murine graft-versus-host disease (GvHD)/graft-versus-leukemia (GvL) models including both MHC-mismatched and miHA-mismatched, the authors demonstrated that treatment with CD115⁺ myeloid-derived suppressor cells efficiently suppressed GvHD but did not significantly impair GvL activity, leading to 80 and 67% protection in treated mice in GvHD and GvL models, respectively. [Leukemia] Abstract

Macrophage β2-Integrins Regulate IL-22 by ILC3s and Protect from Lethal Citrobacter rodentium-Induced Colitis

Using a model of C. rodentium-induced colitis, investigators showed that CD18^−/− mice displayed increased intestinal damage and systemic bacterial burden, compared to littermate controls, ultimately succumbing to infection. [Cell Rep] Full Article | Graphical Abstract

Inhibition of T Cell Activation and Function by the Adaptor Protein CIN85

Researchers showed that Cbl-interacting protein of 85 kDa (CIN85) limited T cell responses to T cell receptor stimulation. Compared to activated wild-type T cells, those that lacked CIN85 produced more IL-2 and exhibited greater proliferation. [Sci Signal] Abstract

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Macrophages as Regulators of Tumor Immunity and Immunotherapy

Macrophages are critical mediators of tissue homeostasis, with tumors distorting this proclivity to stimulate proliferation, angiogenesis and metastasis. This had led to an interest in targeting macrophages in cancer, and preclinical studies have demonstrated efficacy across therapeutic modalities and tumor types. [Nat Rev Immunol] Abstract

Regulation of the Innate Immune System by Autophagy: Monocytes, Macrophages, Dendritic Cells and Antigen Presentation

The authors discuss monocytes/macrophages and dendritic cells, specifically, the influence of autophagy on functional cellular responses, such as phagocytosis, antigen presentation, cytokine production, control of inflammasome activation, tolerance and the consequences for overall host defense. [Cell Death Differ] Abstract

Regulation of the Innate Immune System by Autophagy: Neutrophils, Eosinophils, Mast Cells, NK Cells

The authors reflect on the recent literature pointing to an important role for autophagy in innate immune cells. They focus on neutrophils, eosinophils, mast cells, and natural killer (NK) cells. [Cell Death Differ] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

MaaT Pharma Announces Positive DSMB Safety Review and Continuation of Its Phase II HERACLES Study in Acute GvHD

MaaT Pharma announced that its independent Data and Safety Monitoring Board (DSMB) completed its first safety assessment of the company’s ongoing Phase II HERACLES study with lead biotherapeutic MaaT013 in steroid-resistant, gastrointestinal-predominant, acute graft-versus-host-disease (aGvHD) after allogeneic hematopoietic stem-cell transplantation. [MaaT Pharma] Press Release

Kalytera Reports Additional Positive Data for CBD in Prevention of Acute GvHD

Kalytera Therapeutics, Inc. announced additional positive interim data from its ongoing Phase II clinical study evaluating cannabidiol (CBD) for the prevention of acute graft versus host disease (GvHD) following bone marrow transplant. [Kalytera Therapeutics, Inc.] Press Release

OSE Immunotherapeutics and Servier Announce First Option Within Global License Agreement Exercised for Further Clinical Development and Potential Commercialisation of OSE-127 in Autoimmune Diseases

OSE Immunotherapeutics announced that Servier has exercised the first step under a two-step option agreement for exclusive global rights to OSE-127, a differentiated monoclonal antibody antagonist targeting the interleukin-7 receptor, discovered by OSE. [OSE Immunotherapeutics] Press Release

Equillium Granted U.S. FDA Orphan Drug Designations for EQ001 (Itolizumab) for Both the Prevention and Treatment of Acute Graft-versus-Host Disease

Equillium, Inc. announced that the FDA has granted Orphan Drug designations for EQ001 for both the prevention and treatment of acute graft-versus-host disease. [Equillium, Inc.] Press Release

Incyte Announces U.S. FDA Has Extended the Review Period for Ruxolitinib (Jakafi^®) in Acute Graft-versus-Host Disease

Incyte announced that the FDA has extended the review period for the supplemental New Drug Application for ruxolitinib for the treatment of patients with acute graft-versus-host disease who have had an inadequate response to corticosteroids. [Incyte Corporation] Press Release

The Parker Institute for Cancer Immunotherapy Expands Its Network to Include More Rising Stars in Cancer Immunotherapy

The Parker Institute for Cancer Immunotherapy recently welcomed seven talented early career researchers in cancer immunotherapy to its network as part of the Parker Scholars, Parker Bridge Scholars and Parker Fellows programs. These researchers will receive a total of up to $3.1 million in funding and the opportunity to train with top scientists in the field, to support them as they embark on their research to move the field forward. [The Parker Institute for Cancer Immunotherapy] Press Release

Trump’s $500 Million for Childhood Cancer? Scientists Have Ideas How to Spend It

The pediatric cancer community applauded President Trump’s State of the Union promise of an additional $500 million over the next 10 years to fund research into cures for more childhood cancers. [STAT News] Editorial

NIH Asks Inspector General to Investigate 12 Allegations of Foreign Influence in US Research

The National Institutes of Health (NIH) has referred 12 allegations relating to foreign influence over US-funded research to a federal oversight office, Sen. Chuck Grassley said. Grassley, the chairman of the Senate Finance Committee, has repeatedly demanded information from the NIH after the agency revealed in August it was investigating a half-dozen academic institutions — specifically, researchers who may have failed to disclose financial ties to foreign governments. [STAT News] Editorial

NEW 2019 International Society for Cellular Therapy (ISCT)
May 29-June 1, 2019
Melbourne, Australia

Visit our events page to see a complete list of events in the community.

NEW Research Technologist – Immunology (STEMCELL Technologies Inc.)

NEW Postdoctoral Fellow – Tumor Immune Evasion (Luxembourg Institute of Health)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Staff Scientist – Immunology (Cellzome GmbH)

Assistant Professor – Translational Cancer Research (Texas Tech University Health Sciences Center El Paso)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

PhD Student Position – Immunology (Universitätsmedizin Göttingen)

Postdoctoral Fellow – Immunology (Yonsei Cancer Center)

Postdoctoral Fellowship – Cancer Immunology and Immunotherapy (Columbia Center for Translational Immunology)

Postdoctoral Scientist – Molecular Innate Immunity (Cedars-Sinai Medical Center)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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