Toll-like Receptors 3 and 7 Agonists Enhance Tumor Cell Lysis by Human γδ T Cells
| Autor: | Lothar Marischen, Matthias Juricke, Dieter Kabelitz, Hans-Heinrich Oberg, Hamed Shojaei, Monika Kunz, Christoph Mundhenke, Daniela Wesch, Frank Gieseler |
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| Rok vydání: | 2009 |
| Předmět: |
Cytotoxicity
Immunologic Cancer Research T-Lymphocytes medicine.medical_treatment T cell Antineoplastic Agents chemical and pharmacologic phenomena Antigen Cancer immunotherapy T-Lymphocyte Subsets Cell Line Tumor Neoplasms parasitic diseases MHC class I medicine Humans Cytotoxic T cell Imiquimod biology Histocompatibility Antigens Class I virus diseases Receptors Antigen T-Cell gamma-delta hemic and immune systems T lymphocyte TLR7 Flow Cytometry Coculture Techniques Toll-Like Receptor 3 stomatognathic diseases Poly I-C medicine.anatomical_structure Toll-Like Receptor 7 Oncology Immunology Aminoquinolines Cancer research Granzyme A biology.protein |
| Zdroj: | Cancer Research. 69:8710-8717 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-09-1602 |
| Popis: | 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. [Cancer Res 2009;69(22):8710–7] |
| Databáze: | OpenAIRE |
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