Integrated Discovery of New Immuno-Molecular Actionable Biomarkers for Tumors With Immune-suppressed Environment

Overview

The explosion of novel therapies targeting tumor mutations or immune molecules requests to define or better characterize the mutational profiles of tumors that are none or insufficiently explored so far. This is particularly the case for tumors arising in immune-suppressed individuals or environments which have been poorly, if any, analyzed so far with modern molecular methods. The goal of the translational research program, Ideation, is to define novel biomarkers such as the tumor mutational profiling and immunomutanome in such contexts and to compare the results obtained to those observed in immune competent individuals. In addition, this approach will allow to characterize novel key non-invasive diagnostic and prognostic biomarkers such as circulating tumoral DNA and cells. Altogether results will provide novel biomarkers to better adapt therapeutic strategies in these cancers, to monitor response to treatment as well as to define new molecular targets of potential therapeutic strategies.

The main objective is to discover novel invasive and non-invasive immuno-molecular actionable biomarkers in rare but severe tumors arising in immune-suppressed compared for some tumors in immune-competent patients. Indeed, this tumors present a deficient immune environment, either due to the host acquired immune deficiency, i.e. transplantations or HIV infection, or because the diseased tissue belongs in an immune sanctuary as the brain. The primary hypothesis, in this context, is that these tumor mutational profiles and their changes during drug therapy must be influenced by the immune environment and response. This must lead to differences from similar tumors observed in immune-competent environments (immunocompetent individuals or tissues expressing immunity), responsible for: modification in the molecular targets for appropriate drugs ; alteration of tumor immunogenicity and of future immune-based therapies ; specific biomarkers for monitoring the response to drug therapy. The objectives of this program are to carry on invasive and non-invasive investigations in order to define the mutational profile of these free types of severe tumors, non-Hodgkin lymphoma (NHL), lung cancers and gliomas arising in hosts or tissues with altered immunity. These investigations will lead to : identify novel invasive and non-invasive biomarkers for predicting and evaluating efficacy of future personalized and immune-based therapies; compare tumors from immune-suppressed and immune-competent hosts; discover hot spots of tumoral mutations as mechanisms of tumors resistance, new molecular targets for future molecular and immune-bases therapeutic strategies; define the tumor immunomutanome as a score of neo-epitopes predicting: tumor immunogenicity, disease outcome and efficacy of immunotherapies; detect non-invasive tumoral biomarkers from liquid biopsies based on Circulating tumoral DNA and Circulating tumoral Cells to facilitate future diagnosis and monitoring of such tumors; identify biomarkers of tumor escape or resistance to treatments.