Search

Your search keyword '"Gauthier, Ludiane"' showing total 17 results
Start Over Author "Gauthier, Ludiane"
17 results on '"Gauthier, Ludiane"'

12. Preliminary Data on Safety, Cellular Kinetics and Anti-Leukemic Activity of UCART19, an Allogeneic Anti-CD19 CAR T-Cell Product, in a Pool of Adult and Pediatric Patients with High-Risk CD19+ Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

Author

Benjamin, Reuben, primary, Graham, Charlotte, additional, Yallop, Deborah, additional, Jozwik, Agnieszka, additional, Ciocarlie, Oana, additional, Jain, Nitin, additional, Jabbour, Elias J., additional, Maus, Marcela V., additional, Frigault, Matthiew, additional, Boissel, Nicolas, additional, Larghero, Jerome, additional, Baruchel, Andre, additional, Mohty, Mohamad, additional, De Moerloose, Barbara, additional, Bloor, Adrian, additional, Frey, Noelle V., additional, Zinaï, Amina, additional, Balandraud, Svetlana, additional, Philippe, Anne, additional, Fouliard, Sylvain, additional, Gauthier, Ludiane, additional, Pauly, Jeanne, additional, Konto, Cyril, additional, Bermingham, Candy, additional, Veys, Paul, additional, and Qasim, Waseem, additional

Published
2018
Full Text
View/download PDF

13. Étude de la signalisation de l'intégrine αE(CD103)β7 dans les lymphocytes T cytotoxiques anti-tumoraux

Author

Gauthier, Ludiane, Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Saclay (COmUE), and Fathia Mami-Chouaib

Subjects
Tumor, Signalisation, Intégrine, T cell, [SDV.IMM]Life Sciences [q-bio]/Immunology, hemic and immune systems, chemical and pharmacologic phenomena, Integrin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Lymphocytes T cytotoxiques, Tumeur, Signaling
Abstract

The alphaE(CD103)beta7 integrin plays a crucial role in the formation of a functional immune synapse (IS) between T cells and epithelial target cells. Indeed, the interaction of CD103 on tumor-infiltrating T lymphocyte (TIL) with its ligand, the epithelial cell marker E cadherin on tumor cells, promotes tumor cell killing. We studied CD103 signaling, and we showed that paxillin, a protein found in focal adhesion, interacts with CD103, and its inhibition leads to a decrease in T cell adhesion and spreading of T cell upon activation with immobilized recombinant E-cadherin-Fc. Secondly, we investigated CD103 cytoplasmic domains involved in its activation. Therefore, we used wild-type (WT)-CD103-GFP or various mutant CD103-GFP fusion proteins. Our results showed that ESIRKAQL intracellular motif is necessary for T cell activation, and in particular the serine in position 1163 that is essential for CD103 clustering and paxillin recruitment.; L’étude de l’intégrine alphaE(CD103)beta7, exprimée à la surface des lymphocytes T cytotoxiques (CTL) et ayant pour ligand la E cadhérine, marqueur des cellules épithéliales, a permis de démontrer son rôle dans le recrutement des CTL dans la tumeur, la formation de la synapse immunologique et l'induction de la mort des cellules tumorales épithéliales par les CTL spécifiques. Dans ce contexte, nous avons étudié la signalisation de CD103, et ainsi démontré que la paxilline, une protéine des points d'adhésion focaux, interagit avec CD103. De plus, son inhibition diminue les capacités d'adhésion et d'étalement des CTL sur un tapis d'E cadhérine recombinante humaine. Nous avons ensuite identifié le domaine cytoplasmique de CD103 nécessaire à son activation. Une protéine de fusion CD103-GFP a été construite, ainsi que plusieurs mutants du domaine cytoplasmique de CD103. Nous avons identifié le motif ESIRKAQL, nécessaire à l'activation des lymphocytes T. La sérine en position 1163, présente dans ce motif, semble indispensable à la relocalisation de CD103, des lysosomes et de la paxilline, à la zone de contact avec la E-cadhérine.

Published
2017

17. Paxillin Binding to the Cytoplasmic Domain of CD103 Promotes Cell Adhesion and Effector Functions for CD8 + Resident Memory T Cells in Tumors.

Author

Gauthier L, Corgnac S, Boutet M, Gros G, Validire P, Bismuth G, and Mami-Chouaib F

Subjects
Antigens, CD chemistry, Cell Line, Tumor, Cytoplasm metabolism, HEK293 Cells, Humans, Immunologic Memory physiology, Integrin alpha Chains chemistry, Jurkat Cells, Protein Binding, Protein Interaction Domains and Motifs, Tumor Microenvironment immunology, Antigens, CD metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cell Adhesion, Cytotoxicity, Immunologic physiology, Integrin alpha Chains metabolism, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Paxillin metabolism
Abstract

CD8 + /CD103 + tissue-resident memory T cells (T RM cells) accumulate in several human solid tumors, where they have been associated with a favorable prognosis. However, the role of CD103, the α subunit of the integrin α E β 7 (also known as CD103), in the retention and functions of these T RM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through α E /CD103 chain. Binding to immobilized recombinant (r)E-cadherin-Fc of CD103 integrin expressed on tumor-specific CTL clones promotes phosphorylation of Pxn and Pyk2 and binding of Pxn to the α E /CD103 subunit tail. Inhibition of Pxn phosphorylation by the Src inhibitor saracatinib or its knockdown via shRNA dramatically altered adhesion and spreading of freshly isolated CD8 + /CD103 + lung tumor-infiltrating lymphocytes and CD103 + tumor-specific CTL clones. Inhibition of Pxn phosphorylation with saracatinib in these CTL clones also severely compromised their functional activities toward autologous tumor cells. Using Jurkat T cells as a model to study CD103 integrin activation, we demonstrated a key role of serine residue S1163 of the α E chain intracellular domain in polarization of CD103 and recruitment of lysosomes and Pxn at the contact zone of T lymphocytes with rE-cadherin-Fc-coated beads. Overall, our results show how Pxn binding to the CD103 cytoplasmic tail triggers α E β 7 integrin outside-in signaling that promotes CD8 + T-cell migratory behavior and effector functions. These results also explain the more favorable prognosis associated with retention of T RM cells in the tumor microenvironment. Cancer Res; 77(24); 7072-82. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results