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Translational Researches to Clinics in the field of Oncolmmunology


This axis corresponds to the clinical and translational researches from fundamental and technical development axes which are applied for 2 main projects related to ovarian cancer (OVC) and Glioma (Gliomic).

Since the last 5 years, ovarian cancer pathology (OVC) has been investigated transversally in PRISM by MALDI-MSI and on tissue micro-proteomic. MALDI-MSI was used on ovarian cancer tissue for hunting specific biomarkers and for research on cancer specific markers tubo-ovarian abnormalities proven Pathologists (STIL or STIC) from a tissue bank after prophylactic hysterectomy parts of patients mutated BRCA 1/2. Novel set of biomarkers involve in immune response inhibition and tolerance have been discovered and its etiology investigated. Knowledge of the origin of the different OVC permits well-fitted prophylactic measures. Moreover, the description of molecular specificity of the proteins of each subtype will permit definition of early biomarkers, useful for early diagnosis. Thus, molecular insights will identify therapeutic targets and clinical trials should no longer aggregate the various ovarian types. Our investigation confirm the hypothesis that epithelial ovarian carcinogenesis may occur from Foreign Müllerian cell intrusion into the ovarian environment. Moreover, studies on fimbria of patients mutated BRCA ½ also confirm this hypothesis. Based on these results, therapeutic target has been investigated and the prohormone convertases PACE4 seems a promising one. OVC project is now in two directions i.e. validating MALDI MS molecular signature on large cohort for clinical diagnosis and prognosis in conjunction with the pathologist and macrophages M1 phenotype reactivation in tumor though PC1/3 inhibition. This last part is done in conjunction with Gliomic project by reactivating macrophages type cells in tumor by re-expressing their M1 phenotype by switching from M2 to M1.

Different types of gliomas are identified according to the WHO classification. This classification uses the standard techniques of histopathology. It is based on the one hand the histological type of the tumor and secondly the degree of malignancy. Other classifications are sometimes used, including that of Saint Anne is notable for combining a histopathological analysis of CNS imaging. At present, the management of gliomas remains guided by the WHO classification despite its known limitations. The limits of the WHO classification are largely due to a lack of inter-observer reproducibility but also intra-observer, estimated at 20 to 30%. Moreover, for the same type and the same tumor grade, changes are observed in terms of prognosis. New approaches are absolutely necessary to improve the identification of prognostic factors and response to treatment that could alter the treatment of gliomas. Gliomic is based on mass spectrometry imaging (MSI) technology developed by the laboratory since the last 10 tears (see Technological Development axis). MSI combines technical analysis thus molecular MALDI conventional histology techniques. It is in this sense that one speaks of "molecular histology" to define imaging MALDI-MSI. The aim of Gliomic is to investigate specific protein biomarkers to determine a molecular classification of glioma in adults. In the same time, microglial cells M1 phenotype reactivation is also investigated like in OVC for macrophages through PC1/3 invalidation.