PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer

Abstract

Programmed death 1 ligand 1 (PD-L1) is an immune regulatory molecule that limits antitumor immune activity. Targeting of PD-L1 and other immune checkpoint proteins has shown therapeutic activity in various tumor types. The expression of PD-L1 and its correlation with response to neoadjuvant chemotherapy in breast cancer has not been studied extensively. Our goal was to assess PD-L1 expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. Pretreatment biopsies from 105 patients with breast cancer from Yale New Haven Hospital that subsequently received neoadjuvant chemotherapy were assessed for PD-L1 protein expression by automated quantitative analysis with a rabbit monoclonal antibody (E1L3N) to the cytoplasmic domain of PD-L1. In addition, tumor-infiltrating lymphocytes (TIL) were assessed on hematoxylin and eosin slides. PD-L1 expression was observed in 30% of patients, and it was positively associated with hormone-receptor-negative and triple-negative status and high levels of TILs. Both TILs and PD-L1 measured in the epithelium or stroma predicted pathologic complete response (pCR) to neoadjuvant chemotherapy in univariate and multivariate analyses. However, because they are strongly associated, TILs and PD-L1 cannot both be included in a significant multivariate model. PD-L1 expression is prevalent in breast cancer, particularly hormone-receptor-negative and triple-negative patients, indicating a subset of patients that may benefit from immune therapy. Furthermore, PD-L1 and TILs correlate with pCR, and high PD-L1 predicts pCR in multivariate analysis.

©2014 American Association for Cancer Research.

Figures

Fig 1

Epithelial and stromal PD-L1 expression correlates with pathologic complete response (pCR). (A,B) Distributions of epithelial and stromal PD-L1 expression with quantitative scores for each field of view in two representative cases. A frequency distribution of the epithelial (C) and stromal (D) PD-L1 quantitative scores. Box plots with continuous PD-L1 scores in epithelium (E) and stroma (F) on the Y-axis and pCR or no pCR on the X-axis.

Fig 2

Examples of PD-L1 expression in breast cancers with low and high levels of TILs. Representative H&E and PD-L1 in cases scored non- lymphocyte predominant breast cancer (LPBC) (A,C) and LPBC (B,D). Immunofluorescence images blue=DAPI, green=pan-cytokeratin, red=PD-L1.

Fig 3

Quantitative assessment of epithelial and stromal PD-L1 expression correlates with TILs. Box plots with continuous PD-L1 scores in epithelium (A) and stroma (B) on the Y-axis and lymphocyte predominant breast cancer (LPBC) or non-LPBC on the X-axis.