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Analyses multivariées de la génération de la diversité des cytokines des cellules T CD4 et association de cette diversité aux différents sous types de cancer du sein

Abstract : Today several levels of complexity have emerged in the field of T helper cytokines: 1) the important number of distinct cytokines that Th cell can secrete in various combinations; 2) The multiplicity of signals that can act during Th differentiation to define the Th cytokine secretion profiles 3) The associations of these T helper secretion profiles with complex diseases. During my PhD I focused on these three levels of complexity and study the generation of T helper cytokine diversity and its association to breast cancer subtypes using multivariate analysis and statistical modeling. First, I was able to build the first statistical model linking 37 dendritic cell derived signals to 18 T helper cytokines. Using this model to derive in silico predictions, I was able to found a new role for IL-12p70 as a promoter of Th17 differentiation and as a main differential inducer of IL-17F independently of Il-17A in presence of IL-1. Then, studying the associations of the Th cytokine diversity with the different subtypes of human breast cancers, I found that Th17 cytokines were preferentially associated to Triple Negative Breast Cancer (TNBC). I found that TNBC patients with a high Th17 signature had a better survival. In addition, I showed that Th17 can be combined to clinical prognosis assessment scores, such as the Nottingham Prognosis Index, to better stratify TNBC patients in relevant subgroups for survival prognosis assessment.
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Maximilien Grandclaudon. Analyses multivariées de la génération de la diversité des cytokines des cellules T CD4 et association de cette diversité aux différents sous types de cancer du sein. Immunologie. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS286⟩. ⟨tel-01898867⟩

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