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PLoS One. 2014 Feb 14;9(2):e88557. doi: 10.1371/journal.pone.0088557. eCollection 2014.

PD-L1 expression is increased in a subset of basal type breast cancer cells.

Author information

1
Department of Women's Oncology and Experimental Therapeutics, Moffitt Cancer Center, Tampa, Florida, United States of America.
2
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida, United States of America.
3
Department of Thoracic Oncology and Immunology, Moffitt Cancer Center, Tampa, Florida, United States of America.

Abstract

BACKGROUND:

Tumor cells express programmed death ligand 1 (PD-L1) and is a key immune evasion mechanism. PD-L1 expression in multiple breast cancer cell lines was evaluated to identify intrinsic differences that affect their potential for immune evasion.

METHODS:

PD-L1 expression was analyzed in six breast cancer cell lines: AU565&MCF7 (luminal), BT20&HCC1143 (basal A), MDA231&HCC38 (basal B). Surface and intracellular PD-L1 expression +/- interferon γ for 48 hours was measured by flow cytometry. PD-L1 gene expression data for all breast cancer cell lines in the Comprehensive Cell Line Encyclopedia (CCLE) was analyzed. Correlation between PD-L1 levels and clinicopathologic parameters was analyzed within Oncomine datasets. A tissue microarray containing 61 invasive breast cancer primary tumor cores was stained for PD-L1 expression and analyzed.

RESULTS:

Basal breast cancer cells constitutively express the highest levels of PD-L1. All cell lines increased PD-L1 expression with interferon γ, but basal B cells (MDA-231 and HCC38) demonstrated the largest increases. There were no differences in protein localization between cell lines. In the CCLE data, basal cell lines demonstrated higher mean PD-L1 expression compared to luminal cell lines. High PD-L1 expressing basal cell lines over-express genes involved in invasion, proliferation, and chemoresistance compared to low PD-L1 basal cell lines. High PD-L1 basal cell lines had lower expression of IRF2BP2 and higher STAT1 levels compared to low PD-L1 expressing cell lines. Within Oncomine datasets PDL1 mRNA levels were higher in basal type tumors. The TMA analysis demonstrated that lymph node positive cases had higher levels of PD-L1 protein expression compared to lymph node negative cases.

CONCLUSIONS:

Basal type breast cancer (especially basal B) express greater levels of PD-L1 constitutively and with IFN γ. High PD-L1 basal cells over-express genes involved in invasion, motility, and chemoresistance. Targeting PD-L1 may enhance eradication of aggressive breast cancer cells by the immune system.

PMID:
24551119
PMCID:
PMC3925108
DOI:
10.1371/journal.pone.0088557
[Indexed for MEDLINE]
Free PMC Article

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