We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Blocking MicroRNA Synthesis Reverses Behavior of Tumor-Associated Macrophages

By LabMedica International staff writers
Posted on 22 Jun 2016
Print article
Image: A micrograph showing immune cells (green) attacking tumor cells (red) (Photo courtesy of Dr. Michele De Palma, Ecole Polytechnique Fédérale de Lausanne).
Image: A micrograph showing immune cells (green) attacking tumor cells (red) (Photo courtesy of Dr. Michele De Palma, Ecole Polytechnique Fédérale de Lausanne).
Preventing synthesis of microRNAs in compromised tumor associated macrophages (TAMs) reprograms these cells from being tumor supporting to being tumor suppressing.

TAMs largely express an alternatively activated (or M2) phenotype, which entails immunosuppressive and tumor-promoting capabilities. Reprogramming TAMs towards a classically activated (M1) phenotype might reverse tumor-associated immunosuppression and activate anti-tumor immunity.

To test this possibility, investigators at Ecole Polytechnique Fédérale de Lausanne (Switzerland) used genetic engineering techniques to conditionally delete the microRNA (miRNA)-processing enzyme DICER1 in macrophages. The enzyme Dicer, which is encoded by the DICER1 gene, trims double stranded RNA, to form small interfering RNA (siRNA) or microRNA (miRNA). These processed RNAs are incorporated into the RNA-induced silencing complex (RISC), which targets messenger RNA to prevent translation.

The investigators reported in the June 13, 2016, online edition of the journal Nature Cell Biology that deletion of DICER1 prompted M1-like TAM programming, characterized by hyperactive IFN (interferon)-gamma/STAT1 (signal transducer and activator of transcription 1) signaling. This behavior modification eliminated the immunosuppressive capacity of TAMs and fostered the recruitment of activated cytotoxic T lymphocytes (CTLs) to the tumors. CTL-derived IFN-gamma increased the M1 polarization of DICER1-deficient TAMs and inhibited tumor growth.

Genetic rescue of Let-7 miRNA activity in DICER1-deficient TAMs partly restored their M2-like phenotype and decreased tumor-infiltrating CTLs. These findings suggested that DICER1/Let-7 microRNA activity opposed IFN-gamma-induced, immunostimulatory M1-like TAM activation.

"The most exciting finding was that TAM reprogramming greatly improved the efficacy of immunotherapy," said senior author Dr. Michele De Palma, a tenure track assistant professor at the Ecole Polytechnique Fédérale de Lausanne. "Our results in experimental models of cancer suggest a new therapeutic strategy based on inhibiting the microRNA machinery - or the Let-7 microRNAs - specifically in the TAMs, which may unleash the power of mainstream immunotherapies, such as immune checkpoint inhibitors."

Related Links:
Ecole Polytechnique Fédérale de Lausanne

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
HLX
POCT Fluorescent Immunoassay Analyzer
FIA Go
New
Gold Member
Fully Automated Cell Density/Viability Analyzer
BioProfile FAST CDV

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.