Medical Research Center, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.
Department of Oncology, Jiangyin People's Hospital, Jiangyin, China.
Microbiol Immunol. 2020 Jan;64(1):63-71. doi: 10.1111/1348-0421.12747. Epub 2019 Oct 10.
Specific tumor microenvironment signaling might prevent the maturation of dendritic cells (DCs) with tolerogenic and immunosuppressive potential accounting for antigen-specific unresponsiveness in the lymphoid organs and in the periphery. In the present study, dendritic cells treated with LLC lung cancer cell or 4T1 breast cancer cell culture supernatants significantly down-regulated the expression of co-stimulatory molecules MHC-II, CD40, CD80, but up-regulated the inhibitory molecule PD-L1/L2, VISTA, and increased the messengerRNA levels of interleukin (IL)-6, arginase I, and IL-10, but decreased tumor necrosis factor-α and IL-12a. RNA was isolated from the dendritic cells with or without tumor supernatant stimulation and RNA sequencing was done. Then the differential expression genes were sorted, the candidate genes were analyzed and pathway enrichment analysis was done, and the associated protein-protein interaction network (PPI) was established. After integrated bioinformatical analysis, 405 (279 up-regulated and 126 down-regulated) consistently differential expression genes were identified. Using gene ontology and pathway analysis, it was found that differential expression genes were mainly enriched in the immune response, cell-cell interaction, hemostasis, and cell surface interactions with the vascular wall. The PPI data demonstrated that 236 nodes were classified with 1072 edges, and the most remarkable three modules involved 53 central node genes associated with cell survival, cell-substrate adhesion, chemotaxis, migration, immune response, and complement receptor mediated signaling pathway. These findings revealed the immune status of dendritic cells in the tumor environment.
特定的肿瘤微环境信号可能会阻止树突状细胞 (DCs) 的成熟，具有耐受原性和免疫抑制潜能，从而导致淋巴器官和外周的抗原特异性无反应性。在本研究中，用 LLC 肺癌细胞或 4T1 乳腺癌细胞培养上清液处理的树突状细胞显著下调了共刺激分子 MHC-II、CD40、CD80 的表达，但上调了抑制性分子 PD-L1/L2、VISTA，并增加了白细胞介素 (IL)-6、精氨酸酶 I 和 IL-10 的信使 RNA 水平，但降低了肿瘤坏死因子-α和 IL-12a。从用或不用肿瘤上清液刺激的树突状细胞中分离 RNA，并进行 RNA 测序。然后对差异表达基因进行排序，对候选基因进行分析和通路富集分析，并建立相关的蛋白-蛋白相互作用网络 (PPI)。经过综合生物信息学分析，鉴定出 405 个（279 个上调和 126 个下调）一致差异表达基因。使用基因本体论和通路分析，发现差异表达基因主要富集在免疫反应、细胞-细胞相互作用、止血和细胞表面与血管壁的相互作用中。PPI 数据表明，有 236 个节点分为 1072 个边缘，最显著的三个模块涉及 53 个中心节点基因，与细胞存活、细胞-基质粘附、趋化性、迁移、免疫反应和补体受体介导的信号通路有关。这些发现揭示了肿瘤微环境中树突状细胞的免疫状态。
