PLoS Computational Biology · 2017 · 28 citations · 52 references
MedicineImmunologyOncologyCancer ImmunologyTumor ImmunologyTumor MicroenvironmentCancer ImmunotherapyCancer TranscriptomicsT Cell Responses To TumorsTumor Immune MicroenvironmentTumor Microenvironment InteractionsTumor-stroma InteractionsImmune Gene Expression SignaturesImmune RejectionImmune Signature ProfilingSystemic Immune ResponseTumor Immune Microenvironment ProfilingTumor InteractionsTumor-host Immune InteractionsTumor-immune Crosstalk
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.
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