New discovery on early immune system development

Nov. 12, 2013 — Researchers at Lund University have shed light on how and when the immune system is formed, raising hope of better understanding various diseases in children, such as leukemia.

The immune system is complex and a number of genetic diseases are attributed to defects in the cells that form its origins. The study from Lund and Oxford University presents unique findings on the formation of these cells.

We know that the first blood stem cells are formed in the aorta region and then travel to the liver, which is the body's major blood-forming organ during the fetal stage. In the liver, the blood stem cells produce the more mature blood cells that form our blood system. At the same time, T- and B-cells are formed, which comprise the basis of our advanced immune system. From birth, this process takes place in the bone marrow and the liver ceases to form blood cells.

Researchers have long believed that the first cells that lead to the development of our immune system, the immune-competent cells, are formed from blood stem cells in the liver while the fetus is developing. Blood stem cells can be found in the liver from day 11-12 in a mouse fetus, which is the equivalent of around 6-7 weeks' gestation in humans.

In the current study, which was performed on mice, researchers showed that these cells linked to our immune system are formed even earlier than this, in the embryo's yolk sac, i.e. before the first blood stem cells are formed. In the human embryo, the yolk sac is one of the three fetal sacs and appears in around the fifth week of pregnancy.

"The question we have posed is whether the immune system is formed in a different way in the fetus than in an adult and how early in the development of the fetus the cells that form our early immune system can be found. Knowledge of this is important because it helps us to understand how and when our immune system begins to form and what can go wrong in that process," explained Charlotta Boiers, a postdoctoral fellow at Lund University.

Childhood leukemia is one example of how important it is to understand how the immune system is formed. The first mutation on the path to childhood leukemia has been shown to take place while the child is still in the womb.

"It is still not known in which cell or cells this first step takes place and it is therefore important for us to continue our research on how the immune system starts in humans. The aim is now to continue our investigations in humans," said Charlotta Boiers.

If it is possible to prove that the cells mutate at this very early stage of development, then this would increase our understanding of how childhood leukemia occurs.

"These first cells seem to disappear in the late stages of development of the fetus. This may not happen when there is a mutation. Perhaps the defective cells instead remain alive, and further mutations occur that in turn could lead a child to develop cancer."

View the original article here

Immune system marker tied to improved bone marrow transplant outcomes

Sep. 16, 2013 — The risk of death following bone marrow transplantation can be reduced about 60 percent using a new technique to identify bone marrow donors who make the most potent cancer-fighting immune cells, according to research from St. Jude Children's Research Hospital. The findings appear in the September 16 online issue of the Journal of Clinical Oncology.

The research builds on an earlier St. Jude discovery that specialized immune cells called natural killer (NK) cells dispatched cancer cells more efficiently when the NK cells carried a particular version of a KIR protein on their surface. KIR is short for killer-cell immunoglobulin-like receptor. KIR proteins regulate NK cells.

For this study, researchers reviewed the outcomes of the 313 bone marrow transplants performed at St. Jude during the decade ending in January 2010. Investigators found that patients were far more likely to have survived the transplant and far less likely to had their disease progress if their new bone marrow came from donors whose NK cells included the same version of the protein, rather than the alternative form.

"This approach should dramatically improve the outcome for patients undergoing bone marrow transplantation, regardless of their age or underlying condition," said Wing Leung, M.D., Ph.D., the paper's corresponding author and chair of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. "NK cells also play an important role in autoimmune disorders, chronic infections and other conditions, so these results will likely have an impact beyond cancer."

Transplant patients benefited regardless of their disease, previous treatment, completeness of the genetic match or other donor characteristics, including whether the donor was a relative. Leung said screening for the NK cell variation uses blood collected for the current donor screening process and will not slow donor selection.

NK cells account for less than 15 percent of white blood cells, but play a major role in defending against cancer and viral infections. This research focused on a protein named KIR2DL1, which belongs to the KIR family of proteins. The KIR2DL1 protein is found on NK cells of nearly all healthy individuals.

Proteins are made up of long chains of amino acids. Due to natural genetic variation, there are 25 versions of KIR2DL1, each with a slightly different amino acid sequence.

In an earlier study, Leung and his colleagues discovered that NK cells with one of the KIR2DL1 variations killed cancer cells growing in the laboratory more efficiently than NK cells with a different version of the protein. The potent NK cells featured the amino acid arginine at position 245 of KIR2DL1 rather than the amino acid cysteine in that spot. That discovery led to this study, which offers the first proof that the amino acid difference impacts patient outcomes.

Researchers checked the outcomes of all bone marrow transplants performed at St. Jude during the 10-year period. They found that donor bone marrow with two copies of the gene for the arginine 245 version of KIR2DL1 was associated with a 60 percent decreased risk of death following transplantation and a 62 percent reduced risk of disease progression compared to transplants with donor bone marrow that carried instructions for making just the cysteine version. The transplants involved patients battling both acute lymphoblastic and acute myeloid leukemia as well as other conditions.

St. Jude has patented and licensed a test to identify potential donors with the preferred amino acid. The goal is to make the screening test widely available to other transplant centers as soon as possible, officials said.

View the original article here

Red grapes, blueberries may enhance immune function

Sep. 17, 2013 — In an analysis of 446 compounds for their the ability to boost the innate immune system in humans, researchers in the Linus Pauling Institute at Oregon State University discovered just two that stood out from the crowd -- the resveratrol found in red grapes and a compound called pterostilbene from blueberries.

Both of these compounds, which are called stilbenoids, worked in synergy with vitamin D and had a significant impact in raising the expression of the human cathelicidin antimicrobial peptide, or CAMP gene, that is involved in immune function.

The findings were made in laboratory cell cultures and do not prove that similar results would occur as a result of dietary intake, the scientists said, but do add more interest to the potential of some foods to improve the immune response.

The research was published today in Molecular Nutrition and Food Research, in studies supported by the National Institutes of Health.

"Out of a study of hundreds of compounds, just these two popped right out," said Adrian Gombart, an LPI principal investigator and associate professor in the OSU College of Science. "Their synergy with vitamin D to increase CAMP gene expression was significant and intriguing. It's a pretty interesting interaction."

Resveratrol has been the subject of dozens of studies for a range of possible benefits, from improving cardiovascular health to fighting cancer and reducing inflammation. This research is the first to show a clear synergy with vitamin D that increased CAMP expression by several times, scientists said.

The CAMP gene itself is also the subject of much study, as it has been shown to play a key role in the "innate" immune system, or the body's first line of defense and ability to combat bacterial infection. The innate immune response is especially important as many antibiotics increasingly lose their effectiveness.

A strong link has been established between adequate vitamin D levels and the function of the CAMP gene, and the new research suggests that certain other compounds may play a role as well.

Stilbenoids are compounds produced by plants to fight infections, and in human biology appear to affect some of the signaling pathways that allow vitamin D to do its job, researchers said. It appears that combining these compounds with vitamin D has considerably more biological impact than any of them would separately.

Continued research could lead to a better understanding of how diet and nutrition affect immune function, and possibly lead to the development of therapeutically useful natural compounds that could boost the innate immune response, the researchers said in their report.

Despite the interest in compounds such as resveratrol and pterostilbene, their bioavailability remains a question, the researchers said. Some applications that may evolve could be with topical use to improve barrier defense in wounds or infections, they said.

The regulation of the CAMP gene by vitamin D was discovered by Gombart, and researchers are still learning more about how it and other compounds affect immune function. The unique biological pathways involved are found in only two groups of animals -- humans and non-human primates. Their importance in the immune response could be one reason those pathways have survived through millions of years of separate evolution of these species.

View the original article here

Mechanism discovered in first line of immune defense

Sep. 10, 2013 — Scientists from A*STAR's Singapore Immunology Network (SIgN) have discovered a new defense mechanism that the immune system utilises to combat infections. The team's discovery of how a novel protein unexpectedly activates an immune response shows how this mechanism can also be used to get rid of tumour cells. This research was done in collaboration with University Hospital Basel, Switzerland, published in July 2013 in Nature Immunology.

The immune system combats microbes using several strategies, of which early activation of defence is one of the most important. The mechanisms used by the immune system to counterattack microbes often rely on the immediate recognition of microbes, or of cells that have been affected by the infection of microbes.

The team at SIgN led by Prof Gennaro De Libero has identified a novel mechanism of how the immune system readily detects invading microbes and effectively initiates early immune responses, by activating a special class of cells called gamma delta lymphocytes. Gamma delta lymphocytes were discovered more than 30 years ago and had been identified as cells that are capable of early protection as they play a decisive role in the first line of immune defence. However, many studies into discovering the mechanisms of how these cells are activated when microbes attack have been unfruitful.

The team's discovery of a protein called Butyrophilin 3A1 shows how it binds to microbial antigens and hence activates human gamma delta cells. These cells are then able to coordinate an immune response to clear the infection caused by invading microbes.

This protein has also been found to bind antigens that are produced in large amounts in tumour cells, which then activates gamma delta cells against these tumour cells. The discovery of this mechanism thus represents a novel target that will help to eradicate tumours and combat infections.

Prof De Libero said, "The identification of the molecular mechanisms of how human gamma delta cells get activated opens doors to novel opportunities for immunotherapy of infections and tumours."

Prof Philippe Kourilsky, Chairman of SIgN said, "This study is a breakthrough in immunology and also an excellent example of basic science as an important premise to medicine."

Prof Laurent Renia, Acting Executive Director of SIgN said, "We are delighted that this excellent science has paved the way for many others in immunology and other fields. I believe that these findings present great promise in developing new treatments for cancer therapy and infectious diseases."

View the original article here

Potential immune therapy target for the treatment of malignant melanoma of the identification of seven

Use your own digital technology to count the NCI scientists and tumor tissue of small RNA molecules for identifying melanoma treatment of seven potential immune therapy target. Immunotherapy works by that increase the body's immune system or by using immune cells to attack the cancer cells of a particular type. Overexpression of the success of this treatment for melanoma and cancers of all forms, or very active, is contingent upon finding a protein target cancerous tumor cells have limited expression in normal tissues. 7 That is identified in this work meets the requirements of these gene target. The results of this study led by NCI Division of Cancer Research Center for tumor immunology, surgery branch Morgan Dr. Richard a. 9/10/2013, appeared in clinical cancer research.

Designed a genetic probe containing 97 Morgan and his colleagues looking for a target on the new treatment for malignant melanoma, 72, was considered immune therapy for potential candidate genes and gene sets. Genetic probes for each permit individual RNA molecules accurately count NCI research team, a unique fluorescent barcode had. 59 By using probe isolated researcher in melanoma tumor samples and genetic material RNA to protein, the code sets, and counted each time the barcode gene have been observed. The results of this experiment, scientists concluded 33 of 72 potential target genes overexpression of more than 20% of the malignant melanoma tumor samples. 20 And is expressed in normal tissue samples of tumors of those genes, different methods were identified. Based on this analysis, the researchers conclusions 7 gene warrant potential as a target for immunotherapy of further consideration: found high expression in a large percentage of CSAG2, MAGEA3, MAGEC2 and IL13RA2, PRAME, CSPG4, and SOX10, tumor samples that had limited expression in normal tissues.

View the original article here

Some immune cells appear to aid cancer cell growth

AppId is over the quota
AppId is over the quota

The immune system is normally known for protecting the body from illness. But a subset of immune cells appear to be doing more harm than good. A new study from researchers at the University of Michigan Comprehensive Cancer Center found that these cells, called myeloid derived suppressor cells, provide a niche where the cancer stem cells survive.

Click here to read full press release.

###

Among the research institutions NCI funds across the United States, it currently designates 68 as Cancer Centers. Largely based in research universities, these facilities are home to many of the NCI-supported scientists who conduct a wide range of intense, laboratory research into cancer’s origins and development. The Cancer Centers Program also focuses on trans-disciplinary research, including population science and clinical research. The centers’ research results are often at the forefront of studies in the cancer field.

View the original article here