Abstract
BackgroundTumor 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.MethodsPD-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.ResultsBasal 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.ConclusionsBasal 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.
Highlights
Programmed cell death 1 ligand 1 (PD-L1, CD274, B7-H1) is encoded by the CD274 gene on chromosome nine under the control of an interferon regulatory factor 1 (IRF1) and Signal Transducer Activation of Transcription 1 (STAT1) response elements within its promoter. [1] programmed death ligand 1 (PD-L1) is a 40kDa transmembrane protein that is expressed on a wide variety of normal tissues including natural killer cells, macrophages, myeloid dendritic cells, B cells, epithelial cells, and vascular endothelial cells. [2] Its normal physiologic role is to bind programmed death 1 receptors (PD-1) expressed on the surface of activated cytotoxic T cells
This study identified a subset of basal breast cancer cells lines with much higher PD-L1 expression compared to other basal and luminal cell lines
Both basal B cell lines had the greatest levels of IFNc inducible PD-L1 expression, especially with HCC38 cells
Summary
Programmed cell death 1 ligand 1 (PD-L1, CD274, B7-H1) is encoded by the CD274 gene on chromosome nine under the control of an interferon regulatory factor 1 (IRF1) and Signal Transducer Activation of Transcription 1 (STAT1) response elements within its promoter. [1] PD-L1 is a 40kDa transmembrane protein that is expressed on a wide variety of normal tissues including natural killer cells, macrophages, myeloid dendritic cells, B cells, epithelial cells, and vascular endothelial cells. [2] Its normal physiologic role is to bind programmed death 1 receptors (PD-1) expressed on the surface of activated cytotoxic T cells. [2] Its normal physiologic role is to bind programmed death 1 receptors (PD-1) expressed on the surface of activated cytotoxic T cells. The expression of PD-L1 has been evaluated in a number of different tumor types including breast cancer.[5,6,7] Ghebeh et al reported that PD-L1 expression was associated with a variety of adverse features such as higher grade, negative estrogen receptor status, and increased infiltration with T regulatory cells. Since our understanding of breast cancer biology has evolved with the advent of genomic classification schemes, it is imperative to understand how PD-L1 behaves within different genomic subtypes as well. This is especially important given the fact that while there is overlap between classical and genomic subtypes PD-L1 expression in multiple breast cancer cell lines was evaluated to identify intrinsic differences that affect their potential for immune evasion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
