Immunogenicity as a predictive tool for the response to therapy of high mutation load tumors (IMPRESS)

Project: PN-III-P4-ID-PCE-2016-0870



Cancers with high mutational load, like non-small cell lung cancers (NSCLC) and malignant melanoma (MM), escape from the immune system surveillance, explaining their poor prognostic. Immunotherapy (IT) is trying to overcome the limits of standard therapy and is likely to become a key part of the clinical management of these cancers. But IT doesn’t help everyone and only a subset of patients benefits of it. Immune checkpoint inhibitors are very promising in this setting and specific monoclonal antibodies were approved for clinical use in the treatment of these tumors. However, the clinical results of checkpoint inhibitors blockade have only 15-30% response rate demonstrating that, taken alone, are far from being perfect predictive biomarkers. Available data point towards a strong synergy between radiotherapy (RT) and IT. A crucial and still unsolved issue is the validation of reliable predictive biomarkers. Our aim is to find predictive biomarkers in MM and NSCLC to identify patients who are likely to benefit from IT alone and in combination with other therapies such as RT. We propose a comprehensive, translational and prospective study with 2 arms: experimental and clinical. In the experimental arm, multiple immune molecules at different levels will be evaluated by modern assays and technologies. In the clinical arm, patients with MM and NSCLC treated with standard therapies will be tested for the same markers and their treatment response and outcome will be assessed. This design will allow to correlate the evaluated immune markers with the clinical evolution. The original and innovative aspects of the proposal are: the evaluation and correlation of a large number of potential biomarkers, located in different sites; a comprehensive approach, from the molecular level to the cellular and clinical one, for identification of biomarkers with predictive value for the response to single or combined IT in advanced, poor prognostic cancers.