Oncotarget

Research Papers:

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

Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im and Yeon Hee Park _

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Oncotarget. 2017; 8:47400-47411. https://doi.org/10.18632/oncotarget.17653

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Abstract

Ji-Yeon Kim1,*, Eunjin Lee2,*, Kyunghee Park2, Woong-Yang Park2, Hae Hyun Jung4, Jin Seok Ahn1, Young-Hyuck Im1,3 and Yeon Hee Park1,3,4

1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea

2Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea

3Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea

4Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea

*These authors have contributed equally to this work

Correspondence to:

Yeon Hee Park, email: yhparkhmo@skku.edu

Keywords: breast cancer, immune checkpoint, immune signature, taxane, HER2 expression

Received: October 13, 2016     Accepted: April 24, 2017     Published: May 07, 2017

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.


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