Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy
Toll-like receptors (TLRs), a family of pattern recognition receptors recognizing molecules expressed by pathogens, are typically expressed by immune cells. However, several recent studies revealed functional TLR expression also on tumor cells. Their expressi...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/271246 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832563670411902976 |
|---|---|
| author | Saskia Stier Claudia Maletzki Ulrike Klier Michael Linnebacher |
| author_facet | Saskia Stier Claudia Maletzki Ulrike Klier Michael Linnebacher |
| author_sort | Saskia Stier |
| collection | DOAJ |
| description | Toll-like receptors (TLRs), a family of pattern recognition receptors recognizing molecules expressed by pathogens, are typically expressed by immune cells.
However, several recent studies revealed functional TLR expression also on tumor cells.
Their expression is a two-sided coin for tumor cells.
Not only tumor-promoting effects of TLR ligands are described but also direct oncopathic and immunostimulatory effects.
To clarify TLRs’ role in colorectal cancer (CRC), we tested the impact of the TLR ligands LPS, Poly I:C, R848, and Taxol on primary human CRC cell lines (HROC40, HROC60, and HROC69) in vitro and in vivo (CT26).
Taxol, not only a potent tumor-apoptosis-inducing, but also TLR4-activating chemotherapeutic compound, inhibited growth and viability of all cell lines, whereas the remaining TLR ligands had only marginal effects (R848 > LPS > Poly I:C).
Combinations of the substances here did not improve the results, whereas antitumoral effects were dramatically boosted when human lymphocytes were added.
Here, combining the TLR ligands often diminished antitumoral effects. In vivo, best tumor growth control was achieved by the combination of Taxol and R848.
However, when combined with LPS, Taxol accelerated tumor growth.
These data generally prove the potential of TLR ligands to control tumor growth and activate immune cells, but they also demonstrate the importance of choosing the right combinations. |
| format | Article |
| id | doaj-art-ecb248a98c5447d48d195819217f9f9b |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-ecb248a98c5447d48d195819217f9f9b2025-02-03T01:13:01ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/271246271246Combinations of TLR Ligands: A Promising Approach in Cancer ImmunotherapySaskia Stier0Claudia Maletzki1Ulrike Klier2Michael Linnebacher3Department of General Surgery, Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of General Surgery, Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of General Surgery, Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of General Surgery, Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, GermanyToll-like receptors (TLRs), a family of pattern recognition receptors recognizing molecules expressed by pathogens, are typically expressed by immune cells. However, several recent studies revealed functional TLR expression also on tumor cells. Their expression is a two-sided coin for tumor cells. Not only tumor-promoting effects of TLR ligands are described but also direct oncopathic and immunostimulatory effects. To clarify TLRs’ role in colorectal cancer (CRC), we tested the impact of the TLR ligands LPS, Poly I:C, R848, and Taxol on primary human CRC cell lines (HROC40, HROC60, and HROC69) in vitro and in vivo (CT26). Taxol, not only a potent tumor-apoptosis-inducing, but also TLR4-activating chemotherapeutic compound, inhibited growth and viability of all cell lines, whereas the remaining TLR ligands had only marginal effects (R848 > LPS > Poly I:C). Combinations of the substances here did not improve the results, whereas antitumoral effects were dramatically boosted when human lymphocytes were added. Here, combining the TLR ligands often diminished antitumoral effects. In vivo, best tumor growth control was achieved by the combination of Taxol and R848. However, when combined with LPS, Taxol accelerated tumor growth. These data generally prove the potential of TLR ligands to control tumor growth and activate immune cells, but they also demonstrate the importance of choosing the right combinations.http://dx.doi.org/10.1155/2013/271246 |
| spellingShingle | Saskia Stier Claudia Maletzki Ulrike Klier Michael Linnebacher Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy Clinical and Developmental Immunology |
| title | Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy |
| title_full | Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy |
| title_fullStr | Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy |
| title_full_unstemmed | Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy |
| title_short | Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy |
| title_sort | combinations of tlr ligands a promising approach in cancer immunotherapy |
| url | http://dx.doi.org/10.1155/2013/271246 |
| work_keys_str_mv | AT saskiastier combinationsoftlrligandsapromisingapproachincancerimmunotherapy AT claudiamaletzki combinationsoftlrligandsapromisingapproachincancerimmunotherapy AT ulrikeklier combinationsoftlrligandsapromisingapproachincancerimmunotherapy AT michaellinnebacher combinationsoftlrligandsapromisingapproachincancerimmunotherapy |