Immunological differences between primary and metastatic breast cancer

B Szekely, V Bossuyt, X Li, VB Wali, GA Patwardhan, C Frederick, A Silber, T Park, M Harigopal, V Pelekanou, M Zhang, Q Yan, DL Rimm, G Bianchini, C Hatzis, L Pusztai

Research output: Contribution to journalArticle


Background: Little is known about how the immune microenvironment of breast cancer evolves during disease progression. Patients and methods: We compared tumor infiltrating lymphocyte (TIL) count, programmed death-ligand 1 (PD-L1) protein expression by immunohistochemistry and mRNA levels of 730 immune-related genes using Nanostring technology in primary and metastatic cancer samples. Results: TIL counts and PD-L1 positivity were significantly lower in metastases. Immune cell metagenes corresponding to CD8, T-helper, T-reg, Cytotoxic T, Dendritic and Mastoid cells, and expression of 13 of 29 immuno-oncology therapeutic targets in clinical development including PD1, PD-L1, and CTLA4 were significantly lower in metastases. There was also coordinated down regulation of chemoattractant ligand/receptor pairs (CCL19/CCR7, CXCL9/CXCR3, IL15/IL15R), interferon regulated genes (STAT1, IRF-1,-4,-7, IFI-27,-35), granzyme/granulysin, MHC class I and immune proteasome (PSMB-8,-9,-10) expression in metastases. Immunotherapy response predictive signatures were also lower. The expression of macrophage markers (CD163, CCL2/CCR2, CSF1/CSFR1, CXCR4/CXCL12), protumorigenic toll-like receptor pathway genes (CD14/TLR-1,-2,-4,-5,-6/MyD88), HLA-E, ecto-nuclease CD73/NT5E and inhibitory complement receptors (CD-59,-55,-46) remained high in metastases and represent potential therapeutic targets. Conclusions: Metastatic breast cancers are immunologically more inert than the corresponding primary tumors but some immune-oncology targets and macrophage and angiogenesis signatures show preserved expression and suggest therapeutic combinations for clinical testing.
Original languageEnglish
Pages (from-to)2232-2239
Number of pages8
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Issue number11
Publication statusPublished - 2018


Cite this

Szekely, B., Bossuyt, V., Li, X., Wali, VB., Patwardhan, GA., Frederick, C., Silber, A., Park, T., Harigopal, M., Pelekanou, V., Zhang, M., Yan, Q., Rimm, DL., Bianchini, G., Hatzis, C., & Pusztai, L. (2018). Immunological differences between primary and metastatic breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology, 29(11), 2232-2239.