Immune signature of metastatic breast cancer: Identifying predictive markers of immunotherapy response.

ABSTRACT: In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0.070 and 0.008, respectively). The nine genes associated with immune checkpoints - PDCD1(PD-1), CD274(PD-L1), CD276(B7-H3), CTLA-4, IDO1, LAG3, VTCN1, HAVCR2, and TNFRSF4(OX40) - interacted with each other. In addition, HER2 expression also affected the expression levels of these genes (p = 0.044). Lastly, expression of immune checkpoint genes and tissue-infiltrating lymphocytes were positively correlated in metastatic BCs (p < 0.001). In conclusion, we suggest that HER2 expression and previous taxane treatment are potential surrogate markers for high expression of immune checkpoint genes and immune pathway gene sets. Further study of the BC immune signature with large-scale, translational data sets is warranted.

SUBMITTER: Kim JY 

PROVIDER: S-EPMC5564574 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature