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.
肺癌是全球癌症相关死亡的主要原因。盘状结构域受体1（DDR1）作为一种酪氨酸激酶受体，已被证实与非小细胞肺癌（NSCLC）患者的不良预后相关，但其在肿瘤发生中的作用机制尚不明确。本研究旨在探讨DDR1表达对肺腺癌免疫细胞浸润的影响。研究采用免疫健全的KRAS/p53驱动肺腺癌小鼠模型，通过药物抑制和基因敲除手段干预DDR1功能。将肿瘤细胞皮下移植后，通过流式细胞术分析肿瘤组织的免疫细胞组成。同时利用癌症基因组图谱（TCGA）数据库中509例肺腺癌患者样本进行基因表达分析。实验结果显示，DDR1的药物抑制和基因敲除均导致肿瘤负荷增加，其中DDR1敲除肿瘤中CD8+细胞毒性T细胞减少，而CD4+辅助性T细胞和调节性T细胞增多。TCGA数据分析表明，与高表达DDR1的肿瘤相比，低表达DDR1的肿瘤中调节性T细胞标志物FoxP3表达水平更高。本研究表明，在特定条件下，抑制癌症治疗潜在靶点DDR1可能产生负面效应，例如诱导促肿瘤发生的肿瘤微环境。因此，有必要开展进一步深入研究。
肿瘤(癌症)患者之家