Human Immunology News Volume 8.13 | Apr 7 2020

TOP STORY

A Tale of Two Doctors and One Groundbreaking Cancer Treatment

Two University of Rochester physicians – one as an investigator and one as a patient — had major roles in a cutting-edge clinical trial using the body’s own immune cells to fight late-stage cancer. [Press release from The University of Rochester discussing online prepublication in The New England Journal of Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Microenvironmental Th9- and Th17- Lymphocytes Induce Metastatic Spreading in Lung Cancer

Investigators explored the impact of tumor-infiltrating-lymphocyte subpopulations on lung cancer biology by studying in vitro co-cultures, in vivo mouse models and human lung cancer tissue. Lymphocyte conditioned media- induced epithelial-mesenchymal-transition, and migration in both primary human lung cancer cells and cell lines. [J Clin Invest] Abstract | Full Article | Graphical Abstract

4-1BB Costimulation Promotes CAR T Cell Survival through Noncanonical NF-κB Signaling

Scientists developed a cell-free, ligand-based activation and ex vivo culture system for CD19-specific CAR T cells. They observed greater ex vivo survival and subsequent expansion of BBζ CAR T cells when compared to 28ζ CAR T cells. [Sci Signal] Full Article

Combining Measures of Immune Infiltration Shows Additive Effect on Survival Prediction in High-Grade Serous Ovarian Carcinoma

Epithelium and stroma were semi-automatically segmented and the infiltration of CD45RO⁺, CD8⁺ and CD68⁺ cells was automatically quantified from images of 332 high-grade serous ovarian carcinoma patient tissue microarray cores. [Br J Cancer] Full Article

Diagnostic Value of ¹⁸F-FDG-PET to Predict the Tumor Immune Status Defined by Tumoral PD-L1 and CD8⁺ Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma

The authors performed immunohistochemical analysis of programmed death 1 (PD-L1), hypoxia-inducible factor 1-A, glucose transporter type 1, CD8, E-cadherin and Ki-67 on 59 operable oral squamous cell carcinoma samples. They assessed the correlations between these factors and preoperative 18F-FDG-uptake, clinicopathological characteristics and prognosis. [Br J Cancer] Full Article

Large-Scale Generation of Human Allospecific Induced Tregs with Functional Stability for Use in Immunotherapy in Transplantation

Researchers generated and expand large numbers of allospecific Tregs that maintained stable suppressive function in the presence of pro-inflammatory cytokines. Dendritic cells were derived from monocytes isolated from healthy donors and were co-cultured with CTV-labeled naïve T cells from unrelated individuals, in the presence of TGF-β1, IL-2, and retinoic acid. [Front Immunol] Full Article

Human Chorionic Gonadotropin Modulates CXCL10 Expression through Histone Methylation in Human Decidua

Using in vitro models from decidual samples the authors demonstrated that human chorionic gonadotropin (hCG) inhibited CXCL10 expression by inducing H3K27me3 histone methylation, which bound to region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation was mediated through EZH2, a functional member of the PRC2 complex. [Sci Rep] Full Article

Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Cardiovascular Disease Risk in End-Stage Renal Disease

Plasma leucine-Rich α-2-glycoprotein and high-sensitivity C-reactive protein were analyzed by ELISA in 169 hemodialysis patients from the Immunity in end-stage renal disease study. Patient demographics and comorbidities at the time of enrollment were recorded. [Sci Rep] Full Article

Viral Delivery of CAR Targets to Solid Tumors Enables Effective Cell Therapy

Using CD19 as proof-of-concept, the authors engineered a thymidine kinase disrupted vaccinia virus to selectively deliver CD19 to malignant cells and thus demonstrated potentiation of CD19 CAR T-cell activity against two tumor types in vitro. [Mol Ther Oncolytics] Abstract | Full Article | Graphical Abstract

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Monocytic cell line THP-1 cells were embedded in 3D collagen matrices with different fibril density and were then differentiated into uncommitted macrophages using phorbol-12-myristate-13-acetate. [Bioengineering] Abstract | Download Full Article

Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model

Regenerated WT1-specific cytotoxic T lymphocytes had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma cell line. To make the method more generally applicable, researchers developed an allogeneic approach by transducing HLA-haplotype homozygous induced pluripoten stem cells with WT1-specific TCR α/β genes that had been tested clinically. [iScience] Full Article | Graphical Abstract

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Peripheral T Cell Lymphomas: From the Bench to the Clinic

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of orphan neoplasms. Despite the introduction of anthracycline-based chemotherapy protocols, with or without autologous haematopoietic transplantation and a plethora of new agents, the progression-free survival of patients with PTCLs needs to be improved. [Nat Rev Cancer] Abstract

The Emerging Landscape of Immune Cell Therapies

The authors summarize the current status of immune cell therapies for cancer, infectious disease, and autoimmunity, and discuss advances in cellular engineering to overcome barriers to progress. [Cell] Full Article

T Cell-Engaging Therapies – BiTEs and Beyond

Investigators overview of the current status of bispecific T cell engager (BiTE) therapy, considering the unprecedented new indication for such therapy in combating minimal residual disease in patients with acute lymphoblastic leukemia, and the development of novel approaches based on this concept. [Nat Rev Clin Oncol] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

I-Mab Announces First Patient Dosed in Phase I/IIa Clinical Trial of Anti-CD47 Antibody, TJC4, in China

I-Mab announced that the first patient was dosed with TJC4 in a Phase I/IIa clinical trial evaluating its use in treating patients with relapsed or refractory acute myeloid leukemior myelodysplastic syndrome in China. [I-MAB Biopharma Co., Ltd.] Press Release

Precision BioSciences Announces Dosing of First Patient in Phase I/IIa Clinical Trial of PBCAR20A for Relapsed/Refractory NHL, CLL, and SLL

Precision BioSciences, Inc. announced the initiation of patient dosing in a Phase I/IIa clinical trial of its second off-the-shelf chimeric antigen receptor T cell therapy candidate, PBCAR20A. [Precision BioSciences, Inc.] Press Release

Scientists Around the Globe Pivot Their Research to SARS-CoV-2

Numerous groups around the world have diverted their skills and resources to help stop the pandemic. While the majority of research at academic institutions grinds to a halt, some labs have kept their lights on to conduct coronavirus-related experiments. [The Scientist] Editorial

Safely Conducting Essential Research in the Face of COVID-19

Some scientists can’t simply stop going to their laboratories — especially not those who are overseeing clinical trials that could offer life-saving vaccines and therapies, particularly against the new coronavirus. And some research activities must continue even in the face of a shutdown. [Nature News] Editorial

NIH’s Process for Removing Reviewers Remains a Mystery, Watchdog Finds

A new report by the Office of Inspector General of National Institute of Health’s (NIH’s) parent body, the Department of Health and Human Services, documents how NIH has begun to remove reviews who breached NIH standards on research integrity. [ScienceInsider] Editorial

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NEW 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)

Postdoctoral Researcher – Adoptive T-Cell Therapies (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Moffitt Cancer Center and Research Institute)

Postdoctoral Researchers – B Lymphocyte Regulation (NIH National Institute on Aging)

Research Fellow – Angiogenesis in Immune Regulation and Homing (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Plasma Cell Development (Western Michigan University)

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