Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome

Abstract

Purpose: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in antitumor immune responses. However, there is considerable inconsistency regarding the prognostic value of PD-L1 expression status in breast cancer. We sought to evaluate the differential prognostic impacts of tumoral versus stromal immune cell PD-L1 expression in primary breast cancer. Materials & Methods: Both tumoral and stromal immune PD-L1 expression in formalin-fixed, paraffin-embedded tumor samples from 233 breast cancer patients without initial stage IV metastases were evaluated by immunohistochemistry using a mouse monoclonal anti-PDL1 antibody. Clinicopathological variables were also documented. A Cox regression model was used to assess the association of tumoral/stromal immune PD-L1 expression with clinical outcome using disease-free survival (DFS) as the primary end point. Results: Both tumoral and stromal immune PD-L1 expression were associated with aggressive tumor characteristics, including higher histologic grade, as well as negative estrogen receptor, negative progesterone receptor, and positive human epithelial growth factor receptor 2 (HER2) status Multivariate analyses further demonstrated that stromal immune cell, but not tumoral, PD-L1 expression was a favorable prognostic factor for survival. Conclusions: Despite its association with aggressive tumor features, PD-L1 expression on stromal immune cells emerged as a positive prognostic biomarker in breast cancer. This pro-survival effect might reflect the presence of a strong antitumor immune response that leads to PD-L1 expression.