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Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer

Overview
Journal J Breast Cancer
Date 2016 Oct 11
PMID 27721873
Citations 47
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Abstract

Purpose: 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 (<0.001), negative lymph nodes (=0.011), early pathologic stage (=0.025), high tumor-infiltrating lymphocyte (TIL) (<0.001) counts, negative estrogen receptor (<0.001) and progesterone receptor (=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (=0.003), cytokeratin 5/6 (=0.011), epidermal growth factor receptor (<0.001), and p53 (<0.001) expression, and high Ki-67 proliferating index (<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 (<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (=0.041) and overall survival (OS) (=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; =0.006) and overall death (HR, 3.666; 95% CI, 1.561-8.607; =0.003).

Conclusion: 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.

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References
1.
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G . The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2014; 26(2):259-71. PMC: 6267863. DOI: 10.1093/annonc/mdu450. View

2.
Shin S, Jeon Y, Kim P, Cho Y, Koh J, Chung D . Clinicopathologic Analysis of PD-L1 and PD-L2 Expression in Renal Cell Carcinoma: Association with Oncogenic Proteins Status. Ann Surg Oncol. 2015; 23(2):694-702. DOI: 10.1245/s10434-015-4903-7. View

3.
Phillips T, Simmons P, Inzunza H, Cogswell J, Novotny Jr J, Taylor C . Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer. Appl Immunohistochem Mol Morphol. 2015; 23(8):541-9. PMC: 4561627. DOI: 10.1097/PAI.0000000000000256. View

4.
Baptista M, Sarian L, Derchain S, Pinto G, Vassallo J . Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol. 2015; 47(1):78-84. DOI: 10.1016/j.humpath.2015.09.006. View

5.
Bour-Jordan H, Esensten J, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone J . Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family. Immunol Rev. 2011; 241(1):180-205. PMC: 3077803. DOI: 10.1111/j.1600-065X.2011.01011.x. View