Myeloid-derived suppressor cells (MDSCs) are a population of immune cells that have been implicated in tumour resistance to various types of cancer treatment, including targeted therapies, chemotherapy and immunotherapy. Polymorphonuclear (PMN) cells represent the largest population of MDSCs. However, fully understanding the biology and clinical importance of these cells has been hampered by a lack of markers that set them apart from normal neutrophils.

Now, scientists at The Wistar Institute have identified a marker that distinguishes PMN-MDSCs from neutrophils in the blood of patients with a variety of cancers. Study results showed that higher numbers of cells positive for the marker were associated with larger tumour size.

‘Before we started this work, the only way to isolate PMN-MDSCs was by density centrifugation of blood because they could not be properly identified in tumour tissue,’ said Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor and professor and program leader of the Translational Tumor Immunology program at Wistar, and senior author of the study. ‘Identifying a marker for PMN-MDSCs will allow us to study these cells in much more depth. In addition, if our clinical results are verified in larger studies, the marker could also be used to help physicians and patients make informed treatment decisions and, ultimately, it could be exploited to target PMN-MDSCs for therapeutic benefit.’

MDSCs are potent suppressors of immune responses. They naturally regulate immune responses in healthy individuals, but the population rapidly expands in patients with cancer, and the presence of these cells has been associated with poor patient outcomes. One of the few ways to know for sure that cells are MDSCs is by showing that they suppress immune responses in vitro.

Gabrilovich and colleagues used whole-genome analysis to compare the genes expressed by PMN-MDSCs and neutrophils from the blood of patients with non-small cell lung cancer and head and neck cancer. The researchers focused on the genes expressed at higher levels in PMN-MDSCs compared with neutrophils, in particular those genes that encoded proteins detectable on the surface of cells. This led them to the protein LOX-1, which was almost undetectable on the surface of neutrophils but detectable on the surface of about one-third of PMN-MDSCs.

When they tested the ability of LOX-1-positive and LOX-1-negative cells to suppress immune responses in vitro only the LOX-1-positive cells had this function. The results showed that LOX-1 was a marker of PMN-MDSCs.

Gabrilovich and colleagues speculated that the number of LOX-1-positive PMN-MDSCs in blood and tumour samples from patients with cancer might help predict disease severity and outcome. They had samples from only a few patients with non-small cell lung cancer to study, but found that patients with larger tumours had higher numbers of these cells in both blood and tumour samples.

‘Now that we have a specific marker for MDSCs, we can begin to ask new questions about the biology of these cells and their clinical significance,’ added Gabrilovich.

EurekAlert www.eurekalert.org/pub_releases/2016-08/twi-wsi080316.php

Scientists from the Welcome Trust Sanger Institute and their collaborators have discovered 17 rare human genetic variations associated with risk factors for diseases such as heart disease and diabetes.

The research shows how large-scale genomic datasets can be used to help identify potential novel biological targets for studying cardiovascular and other diseases.

Genetics have been implicated in cardiovascular and blood diseases for some time, however as these are complex diseases, it is extremely difficult to find specific genetic causes. In this study, scientists studied the genomes of almost 36,000 healthy people with European ancestry, looking for rare genetic links to 20 known risk factors for disease, such as raised levels of cholesterol or haemoglobin in the blood.

Two previous large-scale projects provided the whole genome sequences needed: the UK10K project  – a study of the genetic code of 10,000 people that aims to better understand links between rare genetic variations and disease; and the 1000 genome project. From this data, the scientists created a resource called a dense imputation panel, which is freely accessible to the scientific community. The panel holds so much detail that it can fill in the gaps or ‘impute’ data missing from lower resolution genetic studies.

The level of detail the imputation panel provides enabled the scientists to look at specific disease risk factors, and find 17 new genetic variants. Of these, 16 would have been extremely difficult to find without the imputation panel data.

“The dense imputation panel used in this study allowed us to search for genetic variations that are much less frequent than ever before, but that individually explain a greater genetic risk.  As efforts continue to characterise the genetic underpinnings of complex diseases, the methods we have developed in this study are expected to enable the next wave of discoveries of what causes these diseases, and how we might develop new treatments.”

The researchers then applied an analytical technique called fine-mapping to study hundreds of regions of the human genome that contain genetic risk factors for cardiometabolic disease. For 59 regions, they were able to narrow down the most likely genetic causes to small sets of genetic variants. Combining this fine mapping technique with biological data drilled it down even further and provided additional functional insight into the underlying biology.

Sanger Trust www.sanger.ac.uk/news/view/new-genetic-links-heart-disease-risk-factors-identified

People with high levels of good cholesterol, or high-density lipoprotein, are not as safe from heart disease when high levels of a newly identified biomarker of inflammation in the arteries are also found in their bloodstream, according to a new study.

In the study of nearly 3,000 patients, researchers from the Intermountain Medical Center Heart Institute in Salt Lake City discovered that the presence of high levels of the biomarker glycoprotein acetylation, or GlycA, was associated with an increased risk of heart attack or stroke.

Inflammation of the artery walls is a contributing factor to heart attack and stroke because it increases the likelihood that plaque on the arterial walls will rupture, induce clot formation and block blood flow.

“We already know that HDL provides an anti-inflammatory effect on the arteries,” said Brent Muhlestein, MD, co-director of cardiovascular research at the Intermountain Medical Center Heart Institute. “But our research suggests there’s an interaction between GlycA and small HDL particles that reduces the anti-inflammatory capabilities of HDL and increases a person’s chances of having a heart attack or stroke.”

Using a test developed by LipoScience known as NMR spectroscopy, researchers measured lipoprotein particles and GlycA in 2,848 patients whose average age was 63 years old. Sixty-six percent of the patients were male and 65 percent had coronary artery disease.

“The results of our study reinforce the importance of the recommendations we offer to our patients working to reduce inflammation in their arteries by exercising regularly and eating heart-healthy foods,” said Dr. Muhlestein. “Some ways of increasing the HDL levels that will provide the anti-inflammatory protection include eating foods higher in Omega 3s and following the Mediterranean diet, which revolves around plant-based foods, healthy fats, and limited amounts of salt and red meat.”

Historically, C-reactive protein has been used as an indicator of inflammation in the body, and is predictive of future heart-related adverse events. Now, GlycA, a marker of inflammation identified through NMR, appears to show the same predictive ability.

However, researchers are currently seeking to determine if C-reactive protein and GlycA are completely independent of each other in terms of their impact on inflammation and heart disease.

“GlycA is a new particle we didn’t know much about, but now that we know there are epidemiologic associations, we need to look at additional ways to evaluate and understand the way it functions and interacts in the bloodstream,” said Dr. Muhlestein. Intermountain Medical Center Heart Institute

The International Congress on Quality in Laboratory Medicine will be held at Messukeskus, Expo and Convention Centre Helsinki on 9th-10th of February 2017. The annual congress is one of the largest events in Scandinavia focused on quality and laboratory medicine.

The congress inspires medical doctors, pathologists, clinical chemists, biomedical laboratory scientists, medical laboratory experts, managers, quality managers and point-of-care supervisors from the healthcare sector.

The 2017 Congress themes are Impact of Total Quality Management (TQM) and Evidence-Based Laboratory Medicine (EBLM).

Total Quality Management (TQM) is an already more than 60-year old concept that has steadily become more popular in healthcare settings. The idea is to develop a culture which aims at providing patients and customers with products and services that satisfy their needs. In Total Quality Management both management and employees are involved in the continuous improvement of services. It is a combination of quality and management tools to reduce wasteful processes and to avoid errors. In healthcare TQM outcomes are measured by patient health and customer satisfaction.
For healthcare organizations TQM means also a continuous learning process and its base is quantitative, thus being closely related to evidence-based medicine.
Labquality Days 2017 will bring distinguished international speakers together who will highlight the importance of management’s involvement in continuous process improvement. The speakers will also show some concrete examples and tools of TQM in smaller healthcare organizations and in large enterprises.

Evidence-Based Laboratory Medicine (EBLM) is the second theme of the 2017 Congress.
How important are laboratory results in clinical decision making? Are they as valuable in acute myocardial infarction as for a patient suffering from a common cold? Where is the evidence – and do we have enough data to support better patient outcomes?
Choosing the right laboratory test at the right time has become increasingly important particularly in improving and speeding up the diagnostic process and reducing diagnostic errors and costs. The speakers will discuss whether we have enough up-to-date evidence to evaluate the importance of laboratory results, though more controlled well-designed studies are needed.

The International Congress on Quality in Laboratory Medicine will gather leading international speakers and opinion leaders together. The programme consists of scientific lectures and panel discussions. During the congress, participants have the opportunity to meet colleagues, share ideas and experience the extensive clinical laboratory exhibition.

www.labqualitydays.com

Coris BioConcept develops and manufactures immunochromatographic tests allowing fast and accurate diagnosis of infectious diseases. The company was founded by Dr Thierry Leclipteux in 1996, when it was still possible to start a biotech company from scratch. After a lot of determination and support, the first employees were hired only four years later. That moment marked the take-off of the company. Today, 20 years later, Dr Leclipteux and his 30 employees are proud to look back and see how big and  healthy the growth has been. Those 20 years were fueled by the ambition of a never-ending innovation spirit and a worldwide expansion.
Today, Coris BioConcept is a major player in the diagnostic field offering a wide range of effective solutions for the diagnosis  of viruses, bacteria and parasites. When the company started, only two products were available: the Rotavirus and Adenovirus detection tests. Still in the top-10 selling products, these two tests are now included in a total of 50 different products available, all designed and developed in-house. This success could not be reached without continuous investment in research and development. Today, the R&D department represents 40% of the entire working team, which is quite atypical for an SME.
Since the beginning, Coris BioConcept has been increasing and sharing its technical know-how by participating in multiple national and international scientific projects, mainly financed within FP6, FP7 and H2020 framework programmes. Those collaborations combined with the product distribution in more than 60 countries all over the world position Coris BioConcept as an essential player in the diagnostic field. This global involvement motivates the company to set its goals in the development of solutions to major health concerns, such as the fight against antibiotic resistance. This main issue is dramatically evolving in the context of hospital-acquired bacterial infections. Faster diagnostic solutions are required to help clinicians rapidly adopt the most accurate antibiotic treatment. The new “RESIST” range of immunochromatography tests recently launched fulfills that purpose. The NDM-, OXA-48- and KPC-K-SeT allow a precise identification of carbapenem resistant bacteria in less time than conventional laboratory methods. Other additional tests are already under development to offer the most exhaustive set of antibiotic resistances detections.
Coris BioConcept’s challenges for the future have never been that high to maintain its position as an international standard in the infectious diagnostic field. However the company keeps in mind its core values of harmony, rigour, respect and commitment that defines its way of life.

www.corisbio.com