PD-L1 and intratumoral immune response in breast cancer.

Zhi-Qiang Wang,Katy Milne,Brad H Nelson,John R Webb,Heather Derocher,Peter H Watson

doi:10.18632/oncotarget.18305

Abstract

PurposePD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance.MethodsImmunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype.ResultsAcross the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16.5%) cases and associated with known indicators of poor prognosis, including low patient age, high tumor grade, ER/PR negative status, but not with outcome. However, in the Triple Negative breast cancer subset PD-L1 was associated with better recurrence free survival (RFS) especially within the Basal-like subset (Hazard ratio = 0.39, 95% CI = 0.22 - 0.86, p = 0.018). Combined PD-L1/epithelial CD8 positive status was also strongly associated with better RFS and OS (Hazard ratio = 0.12, 95% CI = 0.10 - 0.71, p = 0.010 and Hazard ratio = 0.11, 95% CI = 0.11 - 0.68, p = 0.006 respectively) in the Basal-like subgroup.ConclusionsPD-L1 expression is associated with better patient survival in Basal-like breast cancer.

Highlights

PD-L1 (B7-H1, CD274) is the ligand for Programmed death-1 (PD-1, CD279) and is expressed on the surface of cancer cells in addition to its expression on infiltrating immune cells
In the Triple Negative breast cancer subset PD-L1 was associated with better recurrence free survival (RFS) especially within the Basal-like subset (Hazard ratio = 0.39, 95% CI = 0.22 - 0.86, p = 0.018)
Combined PD-L1/epithelial CD8 positive status was strongly associated with better RFS and overall survival (OS) (Hazard ratio = 0.12, 95% CI = 0.10 - 0.71, p = 0.010 and Hazard ratio = 0.11, 95% CI = 0.11 0.68, p = 0.006 respectively) in the Basal-like subgroup

Summary

Introduction

PD-L1 (B7-H1, CD274) is the ligand for Programmed death-1 (PD-1, CD279) and is expressed on the surface of cancer cells in addition to its expression on infiltrating immune cells. PD-L1 activates PD1 leading to inhibitory signals that regulate T-cell activation and tolerance [1] and impede the antitumor immune response [3, 4]. Recent research has shown that blockade of the interaction between PD-L1 and PD-1 can enhance T cell function and facilitate antitumor activity, and various monoclonal antibodies against PD-1 and PD-L1 are in clinical trials for a variety of solid tumor types, including breast cancer, with encouraging activity in many cancers [5]. PD-L1 expression has been studied as a potential biomarker of response in different types of cancer [6,7,8,9,10,11,12,13,14]. Some studies revealed a negative correlation between PD-L1 expression and outcome [16, 17], while others showed no association with outcome [18, 19] or a positive association with outcome [20,21,22,23]

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