Scientists find new way to get immune cells into tumours
A team of German and Australian scientists has identified a protein which plays a role in keeping tumour-fighting immune cells out of cancerous tumours. The researchers hope that the protein could be used as a target for anti-cancer drugs, especially when used in combination with treatments designed to boost the body's immune response. The work, which is partly funded by the EU, is published online by the journal Nature. Cancerous tumours grow their own blood vessels to ensure a steady supply of oxygen and nutrients. However, unlike ordinary blood vessels, these blood vessels are chaotically structured and regarded as immature. This means that the body's immune cells have difficulties getting into the tumour to fight it. Nevertheless, immune therapies show great promise and when immune cells are able to invade the tumour, patients survive longer. In this latest study, the scientists investigated the role of a signalling protein called Rgs5, which is responsible for keeping the tumour's blood vessels in an immature state. They studied mice suffering from cancer in which the gene responsible for producing Rgs5 had been switched off, and compared these to mice in which the Rgs5 protein was still active. The mice with normal levels of the Rgs5 protein all died by week 35 of the experiment. In contrast, some of the Rgs5-deficient animals were still alive after 48 weeks. Furthermore, when activated immune cells were injected into the Rgs5-deficient mice, they colonised the cancerous tissue in large numbers. Vaccination with tumour-specific proteins also boosted the survival time of the mice. However, when the same treatments were given to mice with normal Rgs5, they had no effect. 'We were surprised that a gene that apparently affects vascular structure has such a strong influence on the success of immune therapies,' commented Professor Günter Hämmerling of the German Cancer Research Centre (DKFZ) in Heidelberg, one of the authors of the study. 'Rgs5 is, thus, a completely new, promising target structure for clinical tumour therapy. But we don't necessarily have to knock out Rgs5 to improve the success of immune therapies. Available therapeutics that normalise tumour vasculature should also increase the invasion of immune cells into tumour tissue.' EU support for the project came from the EU-funded MUGEN ('Integrated functional genomics in mutant mouse models as tools to investigate the complexity of human immunological disease') and CancerImmunoTherapy ('Cancer immunology and immunotherapy') projects, both of which are funded under the 'Life sciences, genomics and biotechnology for health' thematic area of the Sixth Framework Programme (FP6).
Countries
Australia, Germany