Article Date: 02 Sep 2013 – 2:00 PDT
New perspectives against transplant rejection
New scientific results that could one day allow transplanted patients to avoid side effects caused by immunosuppressive therapy were presented at the International Congress of Immunology in Milan. Researchers are testing regulatory cells that can be followed once infused in patients: by doing this, it will be possible to understand if these cells survive and reach their goal, which is convincing the immune system to ignore extraneous tissues coming from the donor. Transplants may save many lives but also require to be followed by life-long treatments, in order to avoid rejection. However, these treatments indiscriminately inhibit the whole organism’s defense, exposing it to the risk of infections and tumors.
The research group led by Maria Grazia Roncarolo, from the San Raffaele Telethon Institute for Gene Therapy, presented new data that confirm, on patients, the results obtained in the laboratory and published on Nature Medicine a few months ago. The anti-rejection approach developed by the researchers is more specific than the one presently employed, since it uses particular regulatory cells – called Tr1 – to block only the immune response that could become dangerous in a specific case, instead of suppressing the whole immune system. “These cells,” explains Maria Grazia Roncarolo, who firstly discovered them when she was working at the DNAX Research Institute of Molecular and Cellular Biology di Palo Alto, in California, “can be used in order to teach the organism to tolerate the transplanted organ, as well as those tissues that become targets for the autoimmune reactions, like in the case of type 1 diabetes.
This strategy has already been tested in bone marrow transplants, where donor’s immune cells, infused in the patient to cure diseases like leukemia and lymphoma, attack the patient himself, in a condition called “graft versus host disease”.
“This is not the only possible therapeutic application for Tr1 cells, since they can induce a specific tolerance that allow the body to defend itself from viruses and bacteria,” continues Roncarolo. “For instance, there are ongoing studies concerning inflammatory intestinal diseases like Crohn’s disease or ulcerative colitis.
Once infused, however, it is necessary to know if the Tr1 cells survive within the organism and continue to carry out their function, keeping the immune system at bay. In the study published on Nature Medicine, some specific markers were described for these cells; it is now known demonstrated that these markers really help to follow Tr1 cells once infused in the patients.
Tr1 regulatory cells are not the only cells that can be used to induce specific tolerance. Many other laboratories all over the world are running experimentations with other types of cells in order to reach the same goal, which could allow to free many patients from side effects due to immunosuppressive therapy and to cure those affected by autoimmune or inflammatory diseases. “Different strategies will be compared in a great European study, called The one study, and will be tested on patients undergoing kidney transplantations with very similar features,” says Roncarolo. Her group is in the front line to demonstrate the efficacy of Tr1 cells.
What’s your score against cancer?
Researchers have developed a test, called Immunoscore, which predicts the ability of a person’s immune system to fight tumor cells. Using Immunoscore as part of routine diagnostic and prognostic assessment may provide crucial novel prognostic information and facilitate clinical decision making (including guiding treatment decisions). The method has been described at ICI 2013 by Jerome Galon, Research Director and Head of the Laboratory of Integrative Cancer Immunology in Paris, that has developed it, defining how the type and characteristics of the immune reaction of the body is associated with prolonged survival of the patients. This issue has just been deepened in a review published by Immunity at the end of July.
The method is based on measuring the number, characterization and localization of different cytotoxic T cells, in charge of killing cancer cells.
In an effort to promote the immunoscore in routine clinical settings, a worldwide task force has been initiated. Led by the Society for Immunotherapy of Cancer (SITC), this task force is comprised of the European Academy of Tumor Immunology, La Fondazione Melanoma and a large number of participating international institutions from 23 centers in 17 different countries (Australia, Austria, Canada, China, Czech Republic, France, Germany, India, Italy, Japan, The Netherlands, Qatar, Spain, Sweden, Switzerland, United Kingdom, United States).
Moreover, another group of scientists led by Dr. Francesco Marincola, who is the Chief Research Officer at Sidra Medical and Research Center of Doha, in Qatar, independently identified some characteristics of tumors that are likely to respond to immunotherapy. The group observed that these characteristics are similar to those displayed by tumors with good prognosis as described by Galon’s group. In particular:
Tumors showing signs of immune activation are more likely to respond to therapy. When they do, their regression is associated with an enhancement of the immune response that was present previously. When tumors regress and are eliminated by the immune system, the immune response is identical to the one observed in other conditions when the immune system plays a role such as rejection of transplants, autoimmunity and clearance of infections. Although the mechanisms of immune response are similar, the responses themselves are different and tissue specific. Therefore, different treatments, which are tailored to treat the specific tissue type, would need to be developed for different conditions. These treatments would all be based on the general principles of immune activation. The realization that these phenomena are based on similar mechanisms may lead to the identification of therapeutic strategies that can integrate information from a range of research fields. This would provide treatments tailored for individual diseases that take into account the repercussions that each treatment may have on other conditions. Public and private for a better health
“Let’s do together what we can’t do on our own.” This could be the right motto for IMI (Innovative Medicines Initiative), which has launched 40 projects to date, on different health issues such as neurological conditions, diabetes, lung disease, oncology, inflammation and infection, tuberculosis, obesity, drug development. In addition to its research projects, IMI also supports a number of education and training projects.
IMI is a European project aimed to stimulate cooperation between public and private research in medicine and has organized a symposium during the 15th International Congress of Immunology now ongoing in Milan, in order to offer an overview on how such a project is pioneering a new way of working in healthcare research.
IMI project started in 2007 and was funded with €1 billion by the European Commission within the Seventh Framework Program (FP7), whilst another €1 billion comes from the member companies of the European Federation of Pharmaceutical Industries and Associations (EFPIA).
Public-private partnerships represent an emerging trend in healthcare research; by bringing together experts from academia, industry, small and medium-sized enterprises, patient groups and regulators, IMI aims to speed up the development of better, safer treatments for patients. To pursue such an objective it is necessary to bridge the gap – conversationally known as “the Valley of Death” – that separates a new discovery from his translation into a new therapy.
IMI’s main objectives have been described during the symposium by Michel Goldman, executive director of the project: developing incentives for healthcare research, pooling initiatives from both public and private institutions and providing a neutral, trusted platform for exchanging data and ideas.
Allied with gut microflora to fight against Candida
Eight people out of ten host Candida Albicans in their gut without any problem, but when the immune defenses are seriously compromised, this fungus can take over and cause severe mycosis that may spread all over the body. Luigina Romani and her colleagues at the University of Perugia just published a new study on the journal Immunity, suggesting how this serious complication could be prevented: “By correlating changes in the metabolite profiles with microbiota metagenomic composition, we have recently defined a functional node by which certain bacteria species contribute to host-microbial symbiosis and mucosal homeostasis in the gut. Switching from sugar to tryptophan as an energy source ⎯ e.g., under conditions of unrestricted tryptophan availability ⎯ highly adaptive lactobacilli were expanded and produced a metabolite capable of affecting local immune homeostasis and fungal control via the cytokine IL-22” .
When Candida starts taking over, a bacteria usually living in our gut, Lactobacillus reuterii, changes its metabolism, switching from sugar to aminoacids as a source of energy. Among these aminoacids, Italian researchers have shown the role of tryptophan, found in chocolate, bananas and dairy products. “Using it as a source of energy, lactobacilli produce an indolic substance, found also in cabbages and broccoli, which induces the synthesis of Interleuchin 22. This explains also conflicting evidence published about probiotic’s efficacy. Not all probiotics are the same nor produce the same effects.
The most important practical implication of this and other studies presented at the conference is in underlining the importance of these bacteria for our health. “This is a further reason not to abuse of antibiotics, especially in immunodepressed patients, who can be damaged by this therapy that deprive them of preciuos allies in the gut” concludes Romani.
Can probiotics help against neurological disorders?
Probiotics can help to reduce the intensity of serious neurologic disorders in rats; this is the interesting result found by an equipe from Besta Institute in Milan, as reported by Chiara Cordiglieri, one of the authors of the work, during the XV International Congress of Immunology in Milan.
Probiotics are viable non-pathogenic bacteria that live in our intestine, like Bifidobacteria, or in our gastric tract, like Lactobacilli. They are able to modify metabolism and modulate the activity of the immune system, thus representing an innovative therapeutic strategy for autoimmune diseases.
Cordiglieri and her colleagues found that Bifidobacterium, which proved to be more effective than Lactobacillus, allowed for a reduction of symptoms and a quicker recovery in rats affected by encephalomyelitis, and a strong decrease in the intensity of the chronic phase in rats suffering from myasthenia gravis.
A high fiber diet protects mice from diabetes
The lack of fiber that characterize the western diet may alter the microbe community that live in our intestine, thus resulting in the increase of the incidence of type 1 diabetes. This is the result of the work presented today at the XV International Congress of Immunology in Milan by Eliana Marino, researcher at the Monash University in Melbourne.
Children with type 1 diabetes have an altered intestinal immune system and it has been hypothesize that is that altered dietary habits in western countries modifies intestinal integrity and corrupts the normal processes of immune tolerance. The gut microflora is known to influence immunity and autoimmunity but this notion has not been taken that seriously. Marino’s work demonstrated that a diet rich in fiber positively influences, through a G-protein receptor, the gut microflora, which in turn improves the activity of the intestinal immune system, thus increasing its efficiency against type 1 diabetes insurgence.