Novel approaches for the treatment of cancer, collectively termed “cancer immunotherapies”, started to reach the clinic in 2011 and are yielding spectacular results, unfortunately only in a limited proportion of patients. Immunotherapeutic reagents aim at stimulating the immune system of cancer patients, to induce destruction of tumor cells by immune effector cells such as anti-tumor T lymphocytes. Monoclonal antibodies that target inhibitory receptors CTLA-4 or PD1 on the surface of T lymphocytes were approved by the FDA and many European countries for the treatment of several types of cancers, including metastatic melanoma and lung adenocarcinomas. Some of these monoclonal antibodies provided impressive clinical benefits to patients, with up to 30-40% patients experiencing tumor regressions, including complete and very long-term rejections. However, a majority of cancer patients still do not respond to available immunotherapies, owing to the existence of potent immunosuppressive mechanisms that paralyse the activity of anti-tumor T lymphocytes within tumor lesions. Our project explores the hypothesis that regulatory T cells (aka Tregs) may exert important immunosuppressive activity on anti-tumor T cells. Our global objective is to generate therapeutic reagents that tamper with the mechanisms by which Tregs suppress other T cells. These reagents could serve as a novel form of immunotherapy, which could be used alone or in combination with existing forms of cancer treatments. Our hope is to develop a novel approach of cancer immunotherapy that is more efficient and less toxic than the currently available treatments. While developing these tools, we also aim at better understanding the fundamental biology which underlies the immunosuppressive functions of Tregs, cells which also play important roles in non-cancerous human diseases such as autoimmunity and chronic infections.
