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Cancer Res. 2011 Jan 15;71(2):328-38. doi: 10.1158/0008-5472.CAN-10-2457. Epub 2011 Jan 11.

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

Author information

1
Institut National de la Santé et de la Recherche Médicale (INSERM) U753, Laboratoire Immunologie des tumeurs humaines: Interaction effecteurs cytotoxiques-système tumoral, Integrated Research Cancer Institute in Villejuif (IRCIV), Institut de Cancérologie Gustave Roussy (IGR), Villejuif, France.

Abstract

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.

PMID:
21224355
DOI:
10.1158/0008-5472.CAN-10-2457
[Indexed for MEDLINE]
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