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Updated: Aug 20, 2026
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Human lung cancer cells express functionally active Toll-like receptor 9
Daniel Droemann1, Dirk Albrecht, Johannes Gerdes
1Medical Clinic, Research Center Borstel, D-23845 Borstel, Germany. ddroemann@fz-borstel.de
Background:
CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology.
Methods:
The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system.
Results:
We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis.
Conclusions:
Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology.
Insights
Toll-like receptor 9 (TLR9) is expressed in lung cancer cells, potentially impacting CpG-oligonucleotide (CpG-ODN) therapies. This finding highlights the active role of malignant cells in tumor immunology.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- CpG-oligonucleotides (CpG-ODN) signal via Toll-like receptor 9 (TLR9) and are explored as cancer and infection adjuvants.
- TLR9 is expressed in immune cells like dendritic cells, B-lymphocytes, and monocytes.
- Investigating TLR9 in tumor cells could refine CpG-ODN treatment strategies and clarify tumor immunology.
Purpose of the Study:
- To determine if bacterial DNA directly interacts with tumor cells.
- To investigate the expression and function of TLR9 in human malignant solid tumors and cell lines.
Main Methods:
- Immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR, and DNA sequencing were used to assess TLR9 expression in lung cancer tissues and cell lines.
- Flow cytometry (FACS) and the Bio-Plex system were employed to detect apoptosis and chemokine expression.
Main Results:
- High TLR9 expression was observed in the cytoplasm of most lung cancer specimens and all tested tumor cell lines.
- Non-malignant lung tissues exhibited only weak and sporadic TLR9 expression.
- CpG-ODN stimulation of cancer cells induced monocyte chemoattractant protein-1 secretion and reduced apoptosis.
Conclusions:
- Toll-like receptor 9 (TLR9) is expressed in human lung cancer tissues and various tumor cell lines.
- Functional TLR9 expression in tumors may influence CpG-ODN treatment approaches.
- Malignant cells can be considered active participants in tumor immunology.
