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.
Highlights
Immune check point inhibitors such as antiprogrammed death-1 (PD-1) and programmed death ligand-1 (PD-L1) antibody are regarded as the “magic bullet” for refractory solid cancer [1, 2]
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)
This study sought to identify an immune signature that would facilitate the development of therapeutic strategies for metastatic breast cancer (BC)
Summary
Immune check point inhibitors such as antiprogrammed death-1 (PD-1) and programmed death ligand-1 (PD-L1) antibody are regarded as the “magic bullet” for refractory solid cancer [1, 2]. They inhibit the interaction between activated T cell immune check point receptors (PD-1) and tumor cell ligand (PD-L1), which facilitates tumor immune evasion [3]. Multiple phase III trials for advanced melanoma, renal cell carcinoma and non-small cell lung cancer (NSCLC) have shown better clinical outcomes for anti-PD-1 antibody than conventional treatment [4,5,6]. In NSCLC, PD-L1 expression in > 50% of tumor cells is correlated with treatment efficacy. PD-L1 expression and mutation signature have not been formally accepted as biomarkers for immunotherapy
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