Final Report Summary - PRR IN IMMUNOTHERAPY (COMBINATIONAL USE OF INNATE IMMUNE RECEPTORS FOR CANCER IMMUNOTHERAPY) Fighting cancer is a major public health challenge in Europe. Activating the immune system to fight cancer has been highly challenging, but tremendous progresses on the use of immune activators have been achieved recently. In this context, the modification of cancer cells such that they acquire features normally limited to pathogens may constitutes a promising new approach because it allows patient immune system to target cancer cells like if they were pathogens. Our work has been focused on developing and improving such a treatment. To approach this issue our group relies on different strategy. The first one consists in identifying new molecules normally express by pathogens such as bacteria and introduce those molecules within tumor cells. These modified tumor cells are then used as vaccines to increase antitumor immunity. A second interest in our laboratory is to finely assess the cellular and molecular events engaged upon detection of bacterial products to better design cancer vaccines. Finally, we are trying to translate our findings into clinically relevant strategies to monitor cancer immune responses and treatment for patients suffering blood borne cancers.Here, we identified a previously unknown cellular adaptation of innate immune cells upon the sensing of live bacteria. We found that macrophages adjust the organization and activity of their mitochondrial respiratory chain in response to the detection of live bacteria. In particular, we discovered that the activity of the complex II, an important component of the respiratory chain, is required for optimal response against bacteria. It allows the production of the metabolite fumarate that exhibits antibacterial properties. In addition, complex II activity is required to fine-tune the innate immune response at the level of cytokines production thereby modulating the balance between inflammatory and tolerant immune response.Our findings will benefits the design of new anticancer molecules and strategies that aim at targeting cancer metabolism. It will also help in the design of next generation vaccines that will includes molecules that modulates immune cell metabolism. Our research is thus beneficial for the European community at several levels since it aims at developing new and low cost vaccines and treatments for cancer and infectious diseases. Therefore, many patients should eventually benefit from our research.
