Tumor microenvironment-derived monoacylglycerol lipase provokes tumor-specific immune responses and lipid profiles

Gruden, Eva; Kienzl, Melanie; Hasenoehrl, Carina; Sarsembayeva, Arailym; Ristic, Dusica; Schmid, Steven M.; Maitz, Kathrin; Taschler, Ulrike; Hahnefeld, Lisa; Thomas, Dominique; Kargl, Julia; Schicho, Rudolf

doi:10.1016/j.plefa.2023.102585

Cited by 1 publication

(1 citation statement)

References 41 publications

(73 reference statements)

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“…Due to the absence of an available EGFR mutant mouse model, we chose to utilize a KRAS/p53-driven model. Accordingly, male C57BL/6J mice were subcutaneously injected with the KP cell line (isolated from LUAD derived from a Kras LSL-G12D Trp53 Fl/Fl mouse with a C57BL/6 background [23,24]) and were treated with 8 mg/kg of the DDR1 inhibitor 7rh or the vehicle via daily intraperitoneal injections (Figure 1A). After 13 days, inhibitor-treated mice surprisingly showed increased ex vivo tumor volume (Figure 1B) and weight (Figure 1C).…”

Section: Inhibition and Knockout Of Ddr1 Drives Tumor Growth In Micementioning

confidence: 99%

Altered Treg Infiltration after Discoidin Domain Receptor 1 (DDR1) Inhibition and Knockout Promotes Tumor Growth in Lung Adenocarcinoma

Maitz,

Valadez-Cosmes,

Raftopoulou

et al. 2023

Cancers

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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.

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Section: Inhibition and Knockout Of Ddr1 Drives Tumor Growth In Micementioning

confidence: 99%

Altered Treg Infiltration after Discoidin Domain Receptor 1 (DDR1) Inhibition and Knockout Promotes Tumor Growth in Lung Adenocarcinoma

Maitz,

Valadez-Cosmes,

Raftopoulou

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

Tumor microenvironment-derived monoacylglycerol lipase provokes tumor-specific immune responses and lipid profiles

Cited by 1 publication

References 41 publications

Altered Treg Infiltration after Discoidin Domain Receptor 1 (DDR1) Inhibition and Knockout Promotes Tumor Growth in Lung Adenocarcinoma

Altered Treg Infiltration after Discoidin Domain Receptor 1 (DDR1) Inhibition and Knockout Promotes Tumor Growth in Lung Adenocarcinoma

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