PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas

SummaryProgrammed death ligand 1 (PD-L1) expression by tumor-infiltrating lymphocytes (TILs) and tumor cells in breast cancer has been reported, but the relationships between PD-L1 expression by TIL, carcinoma cells, and other immunologic features of the breast tumor microenvironment remain unclear. We therefore evaluated the interrelationships between tumor cell surface and TIL PD-L1 expression, lymphocyte subpopulations, and patterns of immune cell infiltration in cohorts of treatment-naive, primary breast cancers (PBCs) (n = 45) and matched PBC and metastatic breast cancers (MBC) (n = 26). Seventy-eight percent of untreated PBCs contained PD-L1+ TILs, but only 21% had PD-L1+ carcinoma cells. Carcinoma PD-L1 expression localized to the tumor invasive front and was associated with high tumor grade (P = .04). Eighty-nine percent of PD-L1+ carcinomas contained brisk TIL infiltrates, compared to only 24% of PD-L1− carcinomas; this included CD3+ (P = .02), CD4+ (P = .04), CD8+ (P = .002), and FoxP3+ T cells (P = .02). PD-L1+ PBCs were more likely to contain PD-L1+ TIL than PD-L1− PBCs (P = .04). Peripheral lymphoid aggregates were present in 100% of PD-L1+ compared to 41% of PD-L1− PBC (P < .001). No patient with PD-L1+ PBC developed distant recurrence, compared to 15% of patients with PD-L1− PBC. For the matched PBC and MBC cohort, 2 patients (8%) had PD-L1+ tumors, with 1 case concordant and 1 case discordant for carcinoma PD-L1 expression in the PBC and MBC. Our data support PD-L1 expression by tumor cells as a biomarker of active breast tumor immunity and programmed death 1 blockade as a therapeutic strategy for breast cancer.