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

Abstract

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

• Authors: Hamed Shojaei, Hans-Heinrich Oberg, Matthias Juricke, Lothar Marischen, Monika Kunz, Christoph Mundhenke, Frank Gieseler, Dieter Kabelitz, Daniela Wesch
• Journal: Cancer research (Cancer Res) Vol. 69 Issue 22 Pg. 8710-7 (Nov 15 2009) ISSN: 1538-7445 [Electronic] United States
• PMID: 19887600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• Antineoplastic Agents
• Histocompatibility Antigens Class I
• Receptors, Antigen, T-Cell, gamma-delta
• TLR3 protein, human
• TLR7 protein, human
• Toll-Like Receptor 3
• Toll-Like Receptor 7
• Poly I-C
• Imiquimod

Topics

• Aminoquinolines (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Coculture Techniques
• Cytotoxicity, Immunologic
• Flow Cytometry
• Histocompatibility Antigens Class I (biosynthesis, drug effects)
• Humans
• Imiquimod
• Neoplasms (drug therapy)
• Poly I-C (pharmacology)
• Receptors, Antigen, T-Cell, gamma-delta (immunology)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes (immunology)
• Toll-Like Receptor 3 (agonists)
• Toll-Like Receptor 7 (agonists)