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Anaplastic thyroid carcinoma (ATC) is a rare and very aggressive disease. Even with multimodality treatment, the prognosis remains very poor with overall survival between 6 and 12 months. Following seminal work from our team, we hypothesize that ATC aggressiveness and resistance to treatments are related to highly immunosuppressive tumoral microenvironment consisting of immunosuppressive myeloid cells and, in particular, tumor-associated macrophages (TAMs). The goal of the PRIMAThyC project is to investigate the profile of circulating and tumor-associated immune cells in the blood and tumor samples of patients with ATC. The expected output of the study is the identification of disease markers that can be used to improve patient’s management and survival, to suggest pathophysiological hypotheses and to identify putative therapeutic targets in order to design new therapeutic strategies. To achieve this goal, the project is composed of 3 tasks: - Mapping: to describe the circulating and tumoral immune landscape of ATC by hogh throuput techniques - Referencing: to identify biomarkers of prognostic and/or therapeutic importance by searching for correlations between candidate biomarkers/immune cell populations and mutational status, pathological characteristics, response to treatments, and overall survival - Validation/modeling: to validate the relevance of the identified biomarkers in vitro and in vivo and by immunohistochemistry on archival tumoral samples. The PRIMAThyC project will deliver an integrative immunological and tumoral map of anaplastic thyroid carcinoma and has the power to identify biomarkers of predictive and/or prognostic interest and new therapeutic targets to design new effective treatment strategies for this very rare deadly disease.
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