title: PD-L1 expression is increased in a subset of basal type breast cancer cells.
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.
authors.affiliation: Department of Women's Oncology and Experimental Therapeutics, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors.forename: Hatem
authors.initials: H
authors.lastname: Soliman
authors.affiliation: Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors.forename: Farah
authors.initials: F
authors.lastname: Khalil
authors.affiliation: Department of Thoracic Oncology and Immunology, Moffitt Cancer Center, Tampa, Florida, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D060890:B7-H1 Antigen; D012333:RNA, Messenger; D007371:Interferon-gamma