This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-09-1602v1 69/22/8710    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Shojaei, H. Articles by Wesch, D. PubMed PubMed Citation Articles by Shojaei, H. Articles by Wesch, D.

Toll-like Receptors 3 and 7 Agonists Enhance Tumor Cell Lysis by Human T Cells

¹ Institute of Immunology, ² Department of Gynecology, and ³ First Department of Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany

Requests for reprints: Daniela Wesch, Institute of Immunology, UK S-H, Campus Kiel, Arnold-Heller Strasse 3, Haus 17, D-24105 Kiel, Germany. Phone: 49-431-5973379; Fax: 49-431-5973335; E-mail: wesch{at}immunologie.uni-kiel.de.

Toll-like receptor (TLR) agonists are considered adjuvants in clinical trials of cancer immunotherapy. Here, we investigated the modulation of T cell–mediated tumor cell lysis by TLR ligands. T-cell cytotoxicity and granzyme A/B production were enhanced after pretreatment of tumor cells with TLR3 [poly(I:C)] or TLR7 ligand (imiquimod). We examined TLR3- and TLR7-expressing pancreatic adenocarcinomas, squamous cell carcinomas of head and neck and lung carcinomas. Poly(I:C) treatment of pancreatic adenocarcinomas followed by coculture with T cells resulted in an upregulation of CD54 on the tumor cells. The interaction of CD54 and the corresponding ligand CD11a/CD18 expressed on T cells is responsible for triggering effector function in T cells. Moreover, treatment with imiquimod downregulated MHC class I molecules on tumor cells possibly resulting in a reduced binding affinity for inhibitory receptor NKG2A expressed on T cells. These results indicate that TLR3 or TLR7 ligand stimulation of tumor cells enhances the cytotoxic activity of expanded T cells of cancer patients in vitro. [Cancer Res 2009;69(22):8710–7]

Key Words: human • T cells • cytotoxicity • poly(I:C) • imiquimod