GYNECO-IMM\&Co is a prospective clinical and biological cohort ; this study aims to identify immune surveillance and escape mechanisms and also predictive biomarkers for survival patients who suffer from ovarian and breast carcinoma.
Breast cancer is the main cancer in women and is the second cause of mortality by cancer in the world for women ; high grade serous ovarian cancer is a rare pathology but survival is less 25% at 5 years. Breast and ovarian cancers are complex entities with heterogeneous tumor cells but also normal cells including immune cells with represent the microenvironment of the tumor.This microenvironment limits tumor progression but also has been shown to play a crucial role in disease progression, tumor angiogenesis, maintenance and resistance to anticancer therapies. Despite newly developed immunotherapies, only one-third of patients with breast and ovarian cancer responds to checkpoint inhibitors ; so today there is poor benefit to treat breast and ovarian cancers with immunotherapies. Therefore it needs to better understand immune mechanisms which reduce treatment efficacy. The aim of this clinical study is to better understand mechanisms of immune response inhibition in breast and ovarian cancers. It would characterize actionable targets in patients with resistance to conventional anticancer treatments or immunotherapies.In this context, the hypothesis is that some specific phenotypical or functional alterations of specific immune cells populations (DC, LB, plasmocytes IgA, neutrophils, NK cells, CD8+CD39+ LT, Treg) induce tumoral progression in breast and ovarian cancer. These immune populations will be described (qualitative, quantitative and functional descriptions ; proteic, transcriptomic and genomic profiles) in order to i) determine new immune surveillance mechanisms ii) new targets which allow efficient antitumoral immunity in breast and ovarian cancers.
Study Type
OBSERVATIONAL
Enrollment
160
Centre Léon Bérard
Lyon, France, France
RECRUITINGCharacterization of immune cells populations on tumour sample from exeresis
Frequency, phenotype and function/activation status of immune cells will be determined by flow cytometry, electrochemiluminescence and proliferation test
Time frame: At surgery
Characterization of immune cells populations on blood sample
Frequency, phenotype and function/activation status of immune cells will be determined by flow cytometry and electrochemiluminescence
Time frame: At surgery
Characterization of transcriptomic profile of immune cells populations
Biomarkers expression, activation or inhibition of functional pathways will be determined by transcriptome sequencing (RNAseq and single cell RNAseq) on tumor sample
Time frame: At surgery
Characterization of molecular profile of tumor sample
Genes profile (Mutation, amplification, insertion, deletion) will be determined by whole exome sequencing (WES)
Time frame: At surgery
Comparison of soluble factors of the tumor microenvironment with soluble factors present in the blood
Comparative characterization (nature and concentration) by Luminex technology MSD
Time frame: At surgery
Characterization of immunoglobulins and their antigenic targets
Characterization by Elisa and Luminex
Time frame: At surgery
Characterization of TCR repertory of LT CD8+ and Tregs
TCR repertory of LT CD8+ and Tregs will be determined by transcriptomic profile by RNAseq
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Time frame: At surgery
Determination of the correlation between biological characterizations at surgery and clinical characterizations
Clinical characterizations are consistent with treatment response and survival ; biological characteristics will describe molecular and transcriptomic profile of the tumor.
Time frame: Up to 60 months