Cancer Immunotherapy involving Natural Killer Cells and Adenosine.

Tumor immunology is a very interesting subset of immunology as the dynamics of the immune system-tumor relationship is a long and very complicated one. Over years and years of cat-and-mouse, many immune evasion techniques have been discovered by researchers. One avenue of evasion is the release of immunosuppressive compounds by the tumor. Although tumor cells release molecules that can be recognized by the immune system and trigger a response (i.e. tumor-specific antigens (TSAs) and tumor associated antigens (TAAs)), these cells are not easy to detect. The tumor cells further ensure that these antigens are not recognized by release of immunosuppressive cytokines like IL-10 and TGF-beta (Mak and Saunders, 2011).

http://en.wikipedia.org/wiki/Metastasis

Another immunosuppressive compound is Adenosine, which is a useful molecule in the body as it is a DNA building block, a component of the main energy source in the body (ATP), and can be used to signal through one of its many receptors (A1, A2A, A2B, and A3). So it goes without saying that adenosine is present, in some form, all over the body.

Previous to the study by Beavis et al (2013), adenosine has been know to be produced from the breakdown of AMP by CD73 - a marker present on many types of cells. It has also been shown that anti-CD73 has resulted in delays in tumor expression, altogether rejection of tumor grafts in mice, inhibiting de novo carcinogensis, and preventing/reducing metastasis. In order to elucidate how exactly this immunosuppressive compound, adenosine, was suppressing tumor growth and metastasis, the authors set out to investigate adenosine in depth.

Pediatric Brain Tumors Exhibit Distinct Phenotypes: Should Therapies Be Individualized?

Tumors are never something to joke around about; they are dangerous, unpredictable, and they can even be fatal. They can appear nearly anywhere in the human body, at basically any point in time. In fact, one of the most dangerous habitats for a tumor is the brain. A complicated and mysterious part of the human body already, the brain controls almost everything, and a tumor appearing in this region can be devastating. They are difficult to remove, and they can have disastrous mental and physical consequences. Even worse, they can present themselves at any age. This makes children susceptible, and what could be worse than that? With around 1,500 children diagnosed a year, pediatric brain tumors are not the most common cause of death in children (1). However, they are the most common type of pediatric tumor, and they have the highest mortality rate over all other childhood cancers. Despite its reputation, this deadly disease has had no improvements regarding treatment methods in the past. Until recently even, the standard treatment was radiation exposure and chemotherapy, which were often coupled with horrible, debilitating side effects. Now, a new form of treatment has been devised due to its tumor specificity – immunotherapy.

"Types of Brain and Spinal Cord Tumors in Children." Johns Hopkins Medicine.
Johns Hopkins University, Hospital, and Health System, 2013. Web. 10 Dec. 2013.

Studies have shown that there have been positive correlations between host immunity and survival rate in children diagnosed with brain tumors. Still, immunotherapy has demonstrated to be largely ineffective due to the immunosuppression induced by brain tumors because it tampers with the immune system-supressing qualities of the exogenous therapy. Several scientists researched pediatric brain tumor types further, however, in order to better understand immunophenotypes – the immunological characteristics – of these tumors. They hoped to shed some light on the subject in order to be able to better treat these afflicted children and give them more of a fighting chance.

               

In Andrea Griesinger and her colleagues’ study, they measured the phenotype and frequency of tumor-infiltrating leukocytes in the four most common types of child brain tumors*(4). They began by surgically taking tumor samples from forty-two patients at the Children’s Hospital in Colorado; they also took five non-tumor samples for a control group. Then, the tissue samples were disaggregated and frozen, before they were eventually suspended, stained, and analyzed via a FACS analysis and a gene expression analysis (2, 3). The FACS analysis then sorted the variety of cells into two or more containers based on their fluorescence while the gene expression analysis quantified the expression levels of certain genes.

             

A New Treatment Option for Alzheimer's Disease? IL Take It!

Alzheimer's disease (AD) is a devastating neurodegenerative disease that is, according to the National Institute on Aging, the most common form of dementia among older people. (1) Dementia is characterized by impairment in many mental faculties including, but not limited to: language, memory and perception. (2) Neuroinflammation is known, at this point in time, to play a role in AD. What exactly inflammation has to do with AD is currently a topic of much debate in scientific circles. An analysis of microarray data using microarray techniques identified 5 cytokines (immune system signals) to be important biomarkers of AD. (3) One of the cytokines identified in that study is IL-1, the production of which has been identified to be critical to the formation of the filamentous protein tangles that are a hallmark of AD. (4) This led a team of researchers at the University of California, Irvine to attempt inhibition of IL-1 signaling in a mouse model of AD with the application of an antibody directed against IL-1R (the receptor for IL-1) with the hope of improving AD symptoms. (5) This study is the focus of this blog post.

The researchers first did a behavioral study to test the efficacy of the antibody treatment on the cognitive abilities of their murine subjects. These mice are not your average laboratory mice; they have had three genes introduced into their cells that result in the accumulation of protein deposits and neuronal miscommunication that plague AD patients. (6) After treatment with the anit-IL-1R antibody, mice showed considerable improvement over non-treated mice in terms of their ability to navigate a water maze and to recall traumatic events (see figure below).

Immunotherapy: Giving Our Bodies a Boost to Fight Infection

The human body’s immune system works tirelessly to keep us healthy. So wouldn’t it be nice if we could lend it a hand in its effort to rid our bodies of all types of pathogens and cancers? Immunotherapy is a type of treatment that seeks to augment our own body’s immune system as it battles certain illnesses and physical conditions. Applications of immunotherapy have been found to be significant in the treatment of cancer, AIDS, autoimmune diseases, and in protecting the body following organ transplantations.

Immunotherapy can be broken down into two main categories: active immunotherapy and passive immunotherapy. Active immunotherapy is designed to stimulate our own immune system so that it can be more effective in combating a disease, such as a cancer vaccine. On the other hand, a passive immunotherapy uses artificially produced components of the immune system, such as antibodies, as a form of treatment. Playing an important role in immunotherapy are certain molecules known as immunomodulators. These molecules, including IL-2, IL-7, IL-12 and interferon, interact with the immune system to induce, enhance, or even suppress the actions of the immune system. More specifically, IL-2 can enhance T, B, and NK cell activation, while IL-7 can promote the development of lymphoid progenitor cells from hematopoietic stem cells. IL-12 is important for the differentiation of ThO cells from naïve T cells and interferon improves antiviral responses. In order to develop new kinds of immunotherapy, researchers must first acquire a sound understanding of how the immune system functions as well as the nature of the particular illness being confronted.