John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Clinical Oncology Department, Nottingham University Hospitals, Nottingham, United Kingdom.
Front Immunol. 2018 Sep 11;9:2028. doi: 10.3389/fimmu.2018.02028. eCollection 2018.
Interactions between the immune system and tumors are highly reciprocal in nature, leading to speculation that tumor recurrence or therapeutic resistance could be influenced or predicted by immune events that manifest locally, but can be detected systemically. Multi-parameter flow cytometry was used to examine the percentage and phenotype of natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), monocyte subsets and regulatory T (Treg) cells in the peripheral blood of of 85 patients with breast cancer (50 of whom were assessed before and after one cycle of anthracycline-based chemotherapy), and 23 controls. Transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) in 23 patients were generated using a NanoString gene profiling platform. An increased percentage of immunosuppressive cells such as granulocytic MDSCs, intermediate CD14CD16 monocytes and CD127CD25FoxP3 Treg cells was observed in patients with breast cancer, especially patients with stage 3 and 4 disease, regardless of ER status. Following neoadjuvant chemotherapy, B cell numbers decreased significantly, whereas monocyte numbers increased. Although chemotherapy had no effect on the percentage of Treg, MDSC and NK cells, the expression of inhibitory receptors CD85j, LIAR and NKG2A and activating receptors NKp30 and NKp44 on NK cells increased, concomitant with a decreased expression of NKp46 and DNAM-1 activating receptors. Transcriptomic profiling revealed a distinct group of 3 patients in the triple negative breast cancer (TNBC) cohort who expressed high levels of mRNA encoding genes predominantly involved in inflammation. The analysis of a large transcriptomic dataset derived from the tumors of patients with TNBC revealed that the expression of predicted relapse-free survival. The peripheral blood immunome of patients with breast cancer is influenced by the presence and stage of cancer, but not by molecular subtypes. Furthermore, immune profiling coupled with transcriptomic analyses of peripheral blood cells may identify patients with TNBC that are at risk of relapse after chemotherapy.
免疫系统和肿瘤之间的相互作用在本质上是高度相互的，这使得人们推测，肿瘤的复发或治疗耐药性可能受到局部表现但可以系统检测到的免疫事件的影响或预测。多参数流式细胞术用于检测 85 例乳腺癌患者（其中 50 例在接受基于蒽环类药物的化疗一个周期前后进行了评估）和 23 例对照者外周血中自然杀伤 (NK) 细胞、髓系来源的抑制细胞 (MDSC)、单核细胞亚群和调节性 T (Treg) 细胞的百分比和表型。使用 NanoString 基因分析平台生成了 23 例患者外周血单个核细胞 (PBMC) 的转录组谱。
无论雌激素受体 (ER) 状态如何，观察到乳腺癌患者，特别是 3 期和 4 期疾病患者，存在更多的免疫抑制性细胞，如粒细胞 MDSC、中间 CD14CD16 单核细胞和 CD127CD25FoxP3 Treg 细胞。新辅助化疗后，B 细胞数量显著减少，而单核细胞数量增加。尽管化疗对 Treg、MDSC 和 NK 细胞的百分比没有影响，但 NK 细胞上抑制性受体 CD85j、LIAR 和 NKG2A 以及激活受体 NKp30 和 NKp44 的表达增加，同时 NKp46 和 DNAM-1 激活受体的表达减少。转录组谱分析显示，三阴性乳腺癌 (TNBC) 队列中有 3 例患者表达高水平的 mRNA，编码主要参与炎症的基因。对来自 TNBC 患者肿瘤的大量转录组数据集的分析表明，表达预测无复发生存率。乳腺癌患者的外周血免疫组受癌症的存在和分期的影响，但不受分子亚型的影响。此外，免疫分析结合外周血细胞的转录组分析可能会识别出化疗后有复发风险的 TNBC 患者。
