Minimal engagement of CD103 on cytotoxic T lymphocytes with an E-cadherin-Fc molecule triggers lytic granule polarization via a phospholipase Cgamma-dependent pathway.

Interaction of the integrin αE(CD103)β7 expressed on tumor-infiltrating lymphocytes (TIL) with E-cadherin on epithelial tumor cells is required to trigger polarized exocytosis of cytotoxic granules in TIL that elicit tumor cell lysis. In this study, we investigated the functional and signaling properties of CD103 and its individual contribution to T-cell-mediated cancer-cell killing. Our results indicated that the binding of CD103 on tumor-specific CTL to immobilized recombinant E-cadherin-Fc is sufficient to induce the polarization of cytolytic granules, whereas the degranulation of cytolytic granules also requires the coengagement of the T-cell receptor. Moreover, minimal CD103 triggering promotes the phosphorylation of the ERK1/2 kinases and phospholipase Cγ1 (PLCγ1). Inhibiting PLCγ blocks granule relocalization, decreasing T-cell receptor-mediated cytotoxicity. Thus, our results emphasize a unique costimulatory role of CD103 in tumor-specific CTL activation by providing signals that promote T-cell effector functions needed to specifically target and lyse cancer cells.

Le Floc'h A ，Jalil A ，Franciszkiewicz K ，Validire P ，Vergnon I ，Mami-Chouaib F ... -  《-》

Alpha E beta 7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis.

Le Floc'h A ，Jalil A ，Vergnon I ，Le Maux Chansac B ，Lazar V ，Bismuth G ，Chouaib S ，Mami-Chouaib F ... -  《-》

Intratumoral induction of CD103 triggers tumor-specific CTL function and CCR5-dependent T-cell retention.

Franciszkiewicz K ，Le Floc'h A ，Jalil A ，Vigant F ，Robert T ，Vergnon I ，Mackiewicz A ，Benihoud K ，Validire P ，Chouaib S ，Combadière C ，Mami-Chouaib F ... -  《-》

CD103 or LFA-1 engagement at the immune synapse between cytotoxic T cells and tumor cells promotes maturation and regulates T-cell effector functions.

Franciszkiewicz K ，Le Floc'h A ，Boutet M ，Vergnon I ，Schmitt A ，Mami-Chouaib F ... -  《-》

Renal allograft rejection: the contribution of chemokines to the adhesion and retention of alphaE(CD103)beta7 integrin-expressing intratubular T cells.

Al-Hamidi A ，Pekalski M ，Robertson H ，Ali S ，Kirby JA ... -  《MOLECULAR IMMUNOLOGY》