Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Thorac Cancer. 2023 Dec;14(34):3369-3380. doi: 10.1111/1759-7714.15128. Epub 2023 Oct 13.
Drug resistance has led to the failure of immunotherapy in triple negative breast cancer patients. Here we aimed to explore the mechanisms of drug resistance in patients in order to enhance their response to immunotherapy.
We downloaded publicly available single-cell RNA-sequencing data of peripheral blood mononuclear cells from patients after treatment to investigate the possible mechanisms of drug resistance. The publicly available TCGA transcriptomic data and somatic mutation data were used for further validation. In this study, a series of bioinformatics and machine learning methods were employed.
We identified the vital roles of CD8+ NKT cells and classical monocytes in the immunotherapy response of triple-negative breast cancer patients. The proportion of these cell types was significantly increased in group partial response. We also found that downregulation of ferroptosis-related genes regulates the immune pathway. The analysis of scRNA data and TCGA transcriptomic data presented that DUSP1 may play a crucial role in immunotherapy resistance.
Overall, the composition of the tumor microenvironment affects the immunotherapy response of patients, and DUSP1 may be a potential target for overcoming drug resistance.
耐药性导致三阴性乳腺癌患者的免疫疗法失败。在这里，我们旨在探索患者耐药的机制，以增强他们对免疫疗法的反应。
我们下载了治疗后患者外周血单个核细胞的公开可用单细胞 RNA 测序数据，以研究可能的耐药机制。进一步验证使用了公开的 TCGA 转录组数据和体细胞突变数据。在这项研究中，使用了一系列生物信息学和机器学习方法。
我们确定了 CD8+NKT 细胞和经典单核细胞在三阴性乳腺癌患者免疫治疗反应中的重要作用。这些细胞类型的比例在部分反应组中显著增加。我们还发现，铁死亡相关基因的下调调节免疫途径。单细胞 RNA 数据和 TCGA 转录组数据的分析表明，DUSP1 可能在免疫治疗耐药中发挥关键作用。
总的来说，肿瘤微环境的组成影响患者的免疫治疗反应，DUSP1 可能是克服耐药性的潜在靶点。
