Interactions between the tumor and the blood systemic response of breast cancer patients

Although systemic immunity is critical to the process of tumor rejection, cancer research has largely focused on immune cells in the tumor microenvironment. To understand molecular changes in the patient systemic response (SR) to the presence of BC, we profiled RNA in blood and matched tumor from 173 patients. We designed a system (MIxT, Matched Interactions Across Tissues) to systematically explore and link molecular processes expressed in each tissue. MIxT confirmed that processes active in the patient SR are especially relevant to BC immunogenicity. The nature of interactions across tissues (i.e. which biological processes are associated and their patterns of expression) varies highly with tumor subtype. For example, aspects of the immune SR are underexpressed proportionally to the level of expression of defined molecular processes specific to basal tumors. The catalog of subtype-specific interactions across tissues from BC patients provides promising new ways to tackle or monitor the disease by exploiting the patient SR.

尽管系统性免疫（systemic immunity）在肿瘤排斥过程中至关重要，但癌症研究长期以来大多聚焦于肿瘤微环境中的免疫细胞。为了解析患者针对乳腺癌（BC）的系统性应答（systemic response, SR）中的分子变化，我们对173名患者的血液及配对肿瘤样本中的RNA进行了表达谱分析。我们开发了一套名为MIxT（跨组织匹配交互，Matched Interactions Across Tissues）的分析系统，用于系统性探究并关联不同组织中表达的分子过程。MIxT证实，患者系统性应答中活跃的分子过程与乳腺癌（BC）的免疫原性（immunogenicity）密切相关。跨组织交互的本质（即存在关联的生物学过程及其表达模式）随肿瘤亚型的不同呈现显著异质性。例如，免疫相关系统性应答的部分特征的表达量，与基底样肿瘤（basal tumors）特有的特定分子过程的表达水平呈负相关。乳腺癌（BC）患者的跨组织亚型特异性交互图谱，为通过利用患者系统性应答来防控或监测该疾病提供了极具前景的新途径。