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 language | English |
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Journal | Cancer Research |
Volume | 69 |
Issue number | 22 |
Pages (from-to) | 8710-8717 |
Number of pages | 8 |
ISSN | 0008-5472 |
DOIs | |
Publication status | Published - 15.11.2009 |