Human Immunology News Volume 8.17 | May 5 2020

TOP STORY

The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans

Researchers examined the anatomic distribution, clonal relationships, and functional properties of T-bet⁺ and T-bet⁻ memory B cells in the context of the influenza-specific immune response. [Immunity] Abstract | Graphical Abstract

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Proimmunogenic Impact of MEK Inhibition Synergizes with Agonist Anti-CD40 Immunostimulatory Antibodies in Tumor Therapy

Investigators showed that targeted inhibition of mitogen-activated protein kinase kinase (MEK) did not impair dendritic cell-mediated T cell priming and activation. Combining MEK inhibitors (MEKi) with agonist antibodies targeting the immunostimulatory CD40 receptor resulted in potent synergistic antitumor efficacy. [Nat Commun] Full Article

N-GSDMD Trafficking to Neutrophil Organelles Facilitates IL-1β Release Independently of Plasma Membrane Pores and Pyroptosis

The authors report that although N-Gasdermin-D (GSDMD) was required for IL-1β secretion in NLRP3-activated human and murine neutrophils, N-GSDMD did not localize to the plasma membrane (PM) or increase PM permeability or pyroptosis. [Nat Commun] Full Article

Pharmacologic PPAR-γ Activation Reprograms Bone Marrow Macrophages and Partially Rescues HSPC Mobilization in Human and Murine Diabetes

Researchers tested a strategy of pharmacologic macrophage reprogramming to rescue hematopoietic stem/progenitor cells (HSPC) mobilization. In vitro, PPAR-γ activation with pioglitazone switched macrophages from M1 to M2, reduced oncostatin M expression, and prevented transcellular induction of Cxcl12. [Diabetes] Full Article

Immune Response and Stromal Changes in Ductal Carcinoma In Situ of the Breast Are Subtype Dependent

The authors included 472 patients with ductal carcinoma in situ (DCIS). The presence of stromal changes, signs of regression, and DCIS-associated immune cell position were determined on hematoxylin and eosin-stained slides. Immune cell composition was characterized by immunohistochemistry. [Mod Pathol] Abstract

LINC01116 Promotes Tumor Proliferation and Neutrophil Recruitment via DDX5-Mediated Regulation of IL-1β in Glioma Cell

Investigators identified that LINC01116 was significantly upregulated in glioma, and positively correlated with clinical malignancy and survival prognosis. LINC01116 regulated the progression of glioma in vitro and in vivo. [Cell Death Dis] Full Article

Anlotinib Alters Tumor Immune Microenvironment by Downregulating PD-L1 Expression on Vascular Endothelial Cells

The authors used the specimens of cancer patients for immunohistochemical staining to observe the number of PD-L1⁺ CD34⁺ vascular endothelial cells and infiltrated immune cells inside tumor specimens. Immunofluorescence staining and flow cytometry were performed to observe the infiltration of CD8⁺ T cells and FoxP3⁺ T cells in tumor tissues. [Cell Death Dis] Full Article

Pre-Clinical Studies of the Off-Target Reactivity of AFP₁₅₈-Specific TCR Engineered T Cells

Researchers conducted in vitro X-scan assay and in silico analysis to determine the off-target cross-reactivity of 3 AFP158-specific human T cells engineered with these TCR genes (TCR-Ts). They found that the three AFP158-specific TCR-Ts could be cross-activated by ENPP1436 peptide and that the TCR3-Ts could also be activated by another off-target peptide, RCL1₂₁₅. [Front Immunol] Full Article

Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit

Scientists identified a number of T cell receptors (TCRs) recognizing the HLA-A*02:01 restricted AFP158−166 peptide FMNKFIYEI, providing a TCR candidate pool for identifying TCRs with optimal clinical benefit. [Front Immunol] Full Article

Electroporation of NKG2D RNA CAR Improves Vγ9Vδ2 T Cell Responses against Human Solid Tumor Xenografts

Investigators adopted a non-viral chimeric antigen receptors (CAR) approach via mRNA electroporation to modify Vγ9Vδ2 T cells and demonstrated that, upon interaction with the NKG2D ligand-positive cancer cells, the CARs substantially enhanced the cytotoxic activity of the modified cells towards multiple cultured solid tumor cell lines, including those resistant to Zometa treatment. [Mol Ther Oncolytics] Abstract | Full Article | Graphical Abstract

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Heterogeneity in the Initiation, Development and Function of Type 2 Immunity

The authors explore how different layers of heterogeneity influence type 2 immunity. Distinct insults, such as allergens or infections, can induce type 2 immune responses through diverse mechanisms, and this can have heterogeneous consequences, ranging from acute or chronic inflammation to deficits in immune regulation and tissue repair. [Nat Rev Immunol] Abstract

Nanomedicines Based on Nanoscale Metal-Organic Frameworks for Cancer Immunotherapy

Scientists summarize recent progress in the development of nanoscale metal-organic frameworks for cancer immunotherapy, including cancer vaccine delivery and combination of in situ vaccination with immunomodulators to reverse immune suppression. [Acta Pharmacol Sin] Abstract

New Directions in Chimeric Antigen Receptor T Cell (CAR-T) Therapy and Related Flow Cytometry

Investigators summarize the current state of CAR T therapy, highlight the areas of emergent research, discuss applications of flow cytometry in modern cell therapy, and touch upon several considerations particular to CAR detection and assessing the effectiveness of CAR T therapy. [Cytometry B Clin Cytom] Abstract

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Editas Medicine Initiates IND-Enabling Activities For EDIT-201, an Allogeneic NK Cell Medicine for the Treatment of Solid Tumor Cancers

Editas Medicine, Inc. announced the initiation of IND-enabling activities for EDIT-201, an allogeneic NK cell medicine for the treatment of solid tumor cancers. [Editas Medicine, Inc.] Press Release

Marker Therapeutics Receives FDA Orphan Drug Designation for its Multi-Antigen Targeted T Cell Therapy for Acute Myeloid Leukemia

Marker Therapeutics, Inc. announced that the FDA Office of Orphan Products Development has granted Orphan Drug designation to MT-401, a multi-tumor-associated antigen-specific T cell product for the treatment of patients with acute myeloid leukemia, following allogeneic stem cell transplant. [Marker Therapeutics, Inc.] Press Release

The Pandemic’s Effects on Recruiting International STEM Trainees

Pandemic-related concerns that have arisen for science trainees—shuttered labs, research and education delays, anxiety—are applicable across the board. But international graduate students and postdocs face a suite of unique challenges that raise uncertainty about recruiting and supporting this critical group of researchers in the future. [The Scientist] Editorial

Students Stand Up for Sub-Contracted Workers amid COVID-19 Crisis

Students at a number of universities have been advocating for the payment of employees, and especially contracted workers who are more vulnerable to layoffs, as campuses shut down during the COVID-19 pandemic. [The Scientist] Editorial

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NEW Postdoctoral Researcher – Oncolytic Virus (ViraTherapeutics GmbH)

Postdoctoral Researcher – DNA Break Repair and Recombination (Fred Hutchinson Cancer Research Center)

Postdoctoral Researcher – Ion Channels in Immunolgoy (New York Univeristy)

Scientist – Post-Injury Inflammation (Athersys, Inc.)

Senior Scientist – Oncology Biomarker Development (Genentech, Inc.)

Associate Professor – Cancer Biology (University of Cincinnati)

Scientist – Cancer Immunology and Immunotherapy (Genentech, Inc.)

Co-Director – Anti-Cancer Immune Response (Rutgers Cancer Institute of New Jersey)

Research Fellow – Mucosal Immunology (University of Michigan)

Faculty Member – Neuro-Oncology (Wake Forest School of Medicine)

Postoctoral Scientist – Molecular and Cellular Immunology (Technical University of Munich)

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