关键词: ILCs T cells paclitaxel chemotherapy single-cell sequence triple-negative breast cancer (TNBC)

Mesh : Humans Paclitaxel / pharmacology therapeutic use Triple Negative Breast Neoplasms / drug therapy genetics metabolism CD8-Positive T-Lymphocytes / metabolism Immunity, Innate Lymphocytes / metabolism

来  源:   DOI:10.3390/ijms241814188   PDF(Pubmed)

Abstract:
Despite the numerous treatments for triple-negative breast cancer (TNBC), chemotherapy is still one of the most effective methods. However, the impact of chemotherapy on immune cells is not yet clear. Therefore, this study aims to explore the different roles of immune cells and their relationship with treatment outcomes in the tumor and blood before and after paclitaxel therapy. We analyzed the single-cell sequencing data of immune cells in tumors and blood before and after paclitaxel treatment. We confirmed a high correlation between T cells, innate lymphoid cells (ILCs), and therapeutic efficacy. The differences in T cells were analyzed related to therapeutic outcomes before and after paclitaxel treatment. In the effective treatment group, post-treatment tumor-infiltrating CD8+ T cells were associated with elevated inflammation, cytokines, and Toll-like-receptor-related gene expression, which were expected to enhance anti-tumor capabilities in tumor immune cells. Moreover, we found that the expression of immune-checkpoint-related genes is also correlated with treatment outcomes. In addition, an ILC subgroup, b_ILC1-XCL1, in which the corresponding marker gene XCL1 was highly expressed, was mainly present in the effective treatment group and was also associated with higher patient survival rates. Overall, we found differences in gene expression in T cells across different groups and a correlation between the expression of immune checkpoint genes in T cells, the b_ILC1-XCL1 subgroup, and patient prognosis.
摘要:
尽管对三阴性乳腺癌(TNBC)有许多治疗方法,化疗仍然是最有效的方法之一。然而,化疗对免疫细胞的影响尚不清楚。因此,本研究旨在探讨紫杉醇治疗前后免疫细胞在肿瘤和血液中的不同作用及其与治疗结局的关系。我们分析了紫杉醇治疗前后肿瘤和血液中免疫细胞的单细胞测序数据。我们证实了T细胞之间的高度相关性,先天淋巴样细胞(ILC),和治疗效果。分析紫杉醇治疗前后T细胞的差异与治疗结果的相关性。在有效治疗组中,治疗后肿瘤浸润性CD8+T细胞与炎症升高相关,细胞因子,和Toll样受体相关基因表达,有望增强肿瘤免疫细胞的抗肿瘤能力。此外,我们发现免疫检查点相关基因的表达也与治疗结局相关.此外,ILC子组,b_ILC1-XCL1,其中相应的标记基因XCL1高表达,主要存在于有效治疗组,也与较高的患者生存率有关。总的来说,我们发现不同组的T细胞中的基因表达存在差异,并且T细胞中免疫检查点基因的表达之间存在相关性,b_ILC1-XCL1子组,和患者预后。
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