Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
Homing of CD8+ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGF-β is responsible for CD103 (αEβ7) integrin induction in activated intraepithelial CD8+ T lymphocytes. However, the interplay between TGF-β and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGF-β enhanced CD103-dependent T-cell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (αLβ2) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGF-β bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation thereby initiating integrin inside-out signaling. Collectively, our findings suggest that the abundance of TGF-β in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer
ISSN: 0008-5472

Droits : info:eu-repo/semantics/OpenAccess
hal-01282442
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282442/file/TGF%CE%B2%20Signaling%20Intersects%20with%20CD103-boutet2016-final.pdf
DOI : 10.1158/0008-5472.CAN-15-1545

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
ISSN: 0168-1923

hal-01086595
https://hal-agroparistech.archives-ouvertes.fr/hal-01086595
DOI : 10.1016/j.agrformet.2009.06.020

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Properly assessing the extent and magnitude of fault ruptures associated with large earthquakes is critical for understanding fault behavior and associated hazard. Submarine faults can trigger tsunamis, whose characteristics are defined by the geometry of seafloor displacement, studied primarily through indirect observations (e.g., seismic event parameters, seismic profiles, shipboard bathymetry, coring) rather than direct ones. Using deep-sea vehicles, we identify for the first time a marker of coseismic slip on a submarine fault plane along the Roseau Fault (Lesser Antilles), and measure its vertical displacement of ∼0.9 m in situ. We also map recent fissuring and faulting of sediments on the hangingwall, along ∼3 km of rupture in close proximity to the fault's base, and document the reactivation of erosion and sedimentation within and downslope of the scarp. These deformation structures were caused by the 2004 M w 6.3 Les Saintes earthquake, which triggered a subsequent tsunami. Their characterization informs estimates of earthquake recurrence on this fault and provides new constraints on the geometry of fault rupture, which is both shorter and displays locally larger coseismic displacements than available model predictions that lack field constraints. This methodology of detailed field observations coupled with near-bottom geophysical surveying can be readily applied to numerous submarine fault systems, and should prove useful in evaluating seismic and tsunamigenic hazard in all geodynamic contexts.
ISSN: 0012-821X

insu-01557932
https://hal-insu.archives-ouvertes.fr/insu-01557932
https://hal-insu.archives-ouvertes.fr/insu-01557932/document
https://hal-insu.archives-ouvertes.fr/insu-01557932/file/EPSL-2006-escartin.pdf
DOI : 10.1016/j.epsl.2016.06.024