TY - JOUR
T1 - Minimal engagement of CD103 on cytotoxic T lymphocytes with an E-cadherin-Fc molecule triggers lytic granule polarization via a phospholipase Cγ-dependent pathway
AU - Le Floc'h, Audrey
AU - Jalil, Abdelali
AU - Franciszkiewicz, Katarzyna
AU - Validire, Pierre
AU - Vergnon, Isabelle
AU - Mami-Chouaib, Fathia
PY - 2011/1/15
Y1 - 2011/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78751500493&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-10-2457
DO - 10.1158/0008-5472.CAN-10-2457
M3 - Article
C2 - 21224355
AN - SCOPUS:78751500493
SN - 0008-5472
VL - 71
SP - 328
EP - 338
JO - Cancer Research
JF - Cancer Research
IS - 2
ER -