title: Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer.
abstract: OBJECTIVE
  The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis.
  
  
  METHODS
  PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas.
  
  
  RESULTS
  High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284-4.445;p=0.006) and overall death (HR, 3.666; 95% CI, 1.561-8.607;p=0.003).
  
  
  CONCLUSIONS
  PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.
authors.affiliation: Department of Hemato-Oncology, Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sang Byung
authors.initials: SB
authors.lastname: Bae
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Hyun Deuk
authors.initials: HD
authors.lastname: Cho
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Mee-Hye
authors.initials: MH
authors.lastname: Oh
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Si-Hyong
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Soon Auck
authors.initials: SA
authors.lastname: Hong
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Junhun
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Hemato-Oncology, Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Han Jo
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
keywords: Breast neoplasms; PD-L1; Prognosis; Tumor-infiltrating lymphocytes