PD-L1 and intratumoral immune response in breast cancer

Abstract

// Zhi-Qiang Wang 1, 4 , Katy Milne 1 , Heather Derocher 1, 2 , John R. Webb 1, 2 , Brad H. Nelson 1, 2, 3 and Peter H. Watson 1, 4 1 Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada 2 Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada 3 Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada 4 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada Correspondence to: Peter H. Watson, email: pwatson@bccancer.bc.ca Keywords: PD-L1, CD4, CD8, CD68, breast cancer Received: March 19, 2017      Accepted: April 28, 2017      Published: May 30, 2017 ABSTRACT Purpose: PD-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. Methods: Immunohistochemistry 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. Results: Across 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. Conclusions: PD-L1 expression is associated with better patient survival in Basal-like breast cancer.