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Microenvironment and Immunology

Minimal Engagement of CD103 on Cytotoxic T Lymphocytes with an E-Cadherin-Fc Molecule Triggers Lytic Granule Polarization via a Phospholipase Cγ–Dependent Pathway

Audrey Le Floc'h, Abdelali Jalil, Katarzyna Franciszkiewicz, Pierre Validire, Isabelle Vergnon and Fathia Mami-Chouaib
Audrey Le Floc'h
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Abdelali Jalil
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Katarzyna Franciszkiewicz
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Pierre Validire
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Isabelle Vergnon
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Fathia Mami-Chouaib
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DOI: 10.1158/0008-5472.CAN-10-2457
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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. Cancer Res; 71(2); 328–38. ©2011 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received July 13, 2010.
  • Revision received October 5, 2010.
  • Accepted November 1, 2010.
  • ©2011 American Association for Cancer Research.
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Published OnlineFirst January 11, 2011
doi: 10.1158/0008-5472.CAN-10-2457

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Minimal Engagement of CD103 on Cytotoxic T Lymphocytes with an E-Cadherin-Fc Molecule Triggers Lytic Granule Polarization via a Phospholipase Cγ–Dependent Pathway
Audrey Le Floc'h, Abdelali Jalil, Katarzyna Franciszkiewicz, Pierre Validire, Isabelle Vergnon and Fathia Mami-Chouaib
Cancer Res January 11 2011 DOI: 10.1158/0008-5472.CAN-10-2457

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Minimal Engagement of CD103 on Cytotoxic T Lymphocytes with an E-Cadherin-Fc Molecule Triggers Lytic Granule Polarization via a Phospholipase Cγ–Dependent Pathway
Audrey Le Floc'h, Abdelali Jalil, Katarzyna Franciszkiewicz, Pierre Validire, Isabelle Vergnon and Fathia Mami-Chouaib
Cancer Res January 11 2011 DOI: 10.1158/0008-5472.CAN-10-2457
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

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