[HTML][HTML] PD-L1 expression is increased in a subset of basal type breast cancer cells

H Soliman, F Khalil, S Antonia - PloS one, 2014 - journals.plos.org
H Soliman, F Khalil, S Antonia
PloS one, 2014journals.plos.org
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 …
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.
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