– ImmuneT-ME

Mature T-cell leukemias/lymphomas (MaTCL) represent a heterogenous group of tumors with predominantly dismal prognoses due to limited efficacy of available treatments. Single MaTCL subtypes are rare, impeding large-volume biomaterial and data collection, and clinical studies. Therapies aimed solely at targeting the tumor cells have failed to extend MaTCL patient survival. Preliminary data from our project partners indicate that MaTCL tumors have alterations in the composition, activation status and tumor-modulating function of the immune microenvironment surrounding the malignant T cells. Our interdisciplinary ‘ImmuneT-ME’ consortium of cancer biologists, clinical hematologists, bioinformaticians and ELSA researchers (e.g. patient organizations) capitalizes on unique resources such as clinical registry linked sample repositories, in-silico machine learning tools, new high-fidelity mouse models and patient advocacy networks. We propose that a comprehensive understanding of the MaTCL immune microenvironment will facilitate the development of new prognostic biomarkers and personalized therapies targeting the tumor microenvironment. We will achieve this in 3 objectives (O): O1 will comprehensively map the immune microenvironment across various MaTCL entities, harnessing omics technologies, large patient datasets, machine learning and clinical sample validation to develop novel, patient stratifying biomarkers. O2 will validate immune microenvironment components as targets for personalized medicine in specific MaTCL entities using primary co-culture systems and preclinical mouse models. O3 will focus on the accelerated implementation of our findings at the levels of patients, peers and other stakeholders, including establishing a European MaTCL patient organization. We anticipate that our project leads to the development of practice-changing decision support systems for microenvironment-targeting personalized therapies in MaTCL, paving the way for future clinical trials.