Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Maitz, K; Valadez-Cosmes, P; Raftopoulou, S; Kindler, O; Kienzl, M; Bolouri, H; Houghton, AM; Schicho, R; Heinemann, A; Kargl, J.
Altered Treg Infiltration after Discoidin Domain Receptor 1 (DDR1) Inhibition and Knockout Promotes Tumor Growth in Lung Adenocarcinoma.
Cancers (Basel). 2023; 15(24): 5767
Doi: 10.3390/cancers15245767
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- Führende Autor*innen der Med Uni Graz
- Kargl Julia
- Maitz Kathrin
- Co-Autor*innen der Med Uni Graz
- Heinemann Akos
- Kienzl Melanie
- Kindler Oliver
- Raftopoulou Sofia
- Schicho Rudolf
- Valadez Cosmes Paulina
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- Abstract:
- Lung cancer is the leading cause of cancer-related death worldwide. Discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor, has been associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). However, its role in tumorigenesis remains poorly understood. This work aimed to explore the impact of DDR1 expression on immune cell infiltration in lung adenocarcinoma. Pharmacological inhibition and knockout of DDR1 were used in an immunocompetent mouse model of KRAS/p53-driven lung adenocarcinoma (LUAD). Tumor cells were engrafted subcutaneously, after which tumors were harvested for investigation of immune cell composition via flow cytometry. The Cancer Genome Atlas (TCGA) cohort was used to perform gene expression analysis of 509 patients with LUAD. Pharmacological inhibition and knockout of DDR1 increased the tumor burden, with DDR1 knockout tumors showing a decrease in CD8+ cytotoxic T cells and an increase in CD4+ helper T cells and regulatory T cells. TCGA analysis revealed that low-DDR1-expressing tumors showed higher FoxP3 (regulatory T-cell marker) expression than high-DDR1-expressing tumors. Our study showed that under certain conditions, the inhibition of DDR1, a potential therapeutic target in cancer treatment, might have negative effects, such as inducing a pro-tumorigenic tumor microenvironment. As such, further investigations are necessary.
- Find related publications in this database (Keywords)
- non-small cell lung cancer
- discoidin domain receptor 1
- tumor microenvironment
- regulatory T cells