Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human γσ T cells

Hamed Shojaei, Hans Heinrich Oberg, Matthias Juricke, Lothar Marischen, Monika Kunz, Christoph Mundhenke, Frank Gieseler, Dieter Kabelitz, Daniela Wesch*

*Corresponding author for this work
72 Citations (Scopus)

Abstract

Toll-like receptor (TLR) agonists are considered adjuvants in clinical trials of cancer immunotherapy. Here, we investigated the modulation of γδ T cell-mediated tumor cell lysis by TLR ligands. γδ 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 γδ T cells resulted in an upregulation of CD54 on the tumor cells. The interaction of CD54 and the corresponding ligand CD11a/CD18 expressed on γδ T cells is responsible for triggering effector function in γδ 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 γδ T cells. These results indicate that TLR3 or TLR7 ligand stimulation of tumor cells enhances the cytotoxic activity of expanded γδ T cells of cancer patients in vitro.

Original languageEnglish
JournalCancer Research
Volume69
Issue number22
Pages (from-to)8710-8717
Number of pages8
ISSN0008-5472
DOIs
Publication statusPublished - 15.11.2009

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