Immunomodulatory pathways in both breast cancer and placental tissues: Insights from a unique clinical and genomic case report.

Abstract

13 Background: some cancers might partially ectopically express intrinsic immune escape gene programs naturally developed during mammalian evolution to allow for materno-fetal immune tolerance. Methods: Genomic analysis (Nanostring Inc, Seattle, WA, USA) was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman (same patient). Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Results: Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (placenta) and pathologically ( cancer). Placenta and uterus, breast tissues (tumor and normal) and lymph node tissues (tumor and normal) formed their own RNA transcription cluster, suggesting that tissue specific gene expression patterns were well preserved during experimental procedures . We analyzed differential expression within each tissue type (i.e. matching for the analysis placenta with uterus, breast cancer with normal breast tissue and node positive with node negative tissue). Among the 583 genes analyzed, 103 genes were upregulated > 1.5 fold in placenta versus uterus, while 258 genes were downregulated at least 1.5 fold. Using the same cut-off, 258 genes were upregulated and 44 genes downregulated in breast tumor versus normal breast tissue, and 178 genes were upregulated while 146 genes downregulated in tumor bearing lymph node versus non-involved lymph node. Conclusions: A variety of complex immune regulation mechanisms seem to be shared by both placental tissues and cancer.