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Theses

Hétérogénéité et mécanismes d’initiation de la réponse humorale dans les tumeurs du sein et de l’ovaire

Abstract : B and plasma cells are rising as crucial cells in the immune surveillance of tumors, even though their pro- or anti-tumor role is still debated. We argue that this dual functionality of B cells could depend on the identity of tumor-infiltrating B cell subsets and/or by the nature of the antibodies they produce. With that knowledge, we showed that breast and ovarian tumors are usually infiltrated by memory B cells and plasma cells that express and/or produce mainly IgG or IgA. This last class of Ig in highly enriched in in situ carcinomas of the breast, corresponding to earlier tumors, and in 15-20% of invasive tumors, suggesting a differential role of IgG and IgA in tumor progression. IgA, that can be monomeric or dimeric in tumors, often target antigens that differ from those targeted by IgG. We also show that antigens targeted by IgA and IgG in the tumor are often involved in functions related to the development of tissues and DNA interactions, and can be share amongst patients and between breast and ovarian tumors, suggesting their importance in the anti-tumor immune response. In parallel, using tumors from patients suffering from a paraneoplastic neurological syndrome, we established that the concomitant induction of IgG PC and CD8+ cytotoxic T cells in the tumor is associated wth amplifications and/or mutations in the genes of tumor antigens. These results highlight the importance of B cells and Ig in the anti-tumor immune response and give leads to look for new targets in immunotherapy
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https://tel.archives-ouvertes.fr/tel-02463459
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Coline Couillault. Hétérogénéité et mécanismes d’initiation de la réponse humorale dans les tumeurs du sein et de l’ovaire. Immunologie. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSE1051⟩. ⟨tel-02463459⟩

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