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

• Published in: Human pathology Vol. 47; no. 1; pp. 52 - 63
• Main Authors: Cimino-Mathews, Ashley, MD, Thompson, Elizabeth, MD, PhD, Taube, Janis M., MD, Ye, Xiaobu, MD, Lu, Yao, MS, Meeker, Alan, PhD, Xu, Haiying, BS, Sharma, Rajni, PhD, Lecksell, Kristen, MS, Cornish, Toby C., MD, PhD, Cuka, Nathan, MD, Argani, Pedram, MD, Emens, Leisha A., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Aggregates; B7-H1 Antigen - analysis; Biomarkers, Tumor - analysis; Breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Carcinoma - chemistry; Carcinoma - immunology; Carcinoma - pathology; Carcinoma - therapy; Chemotherapy; Epidermal growth factor; Female; Gene expression; Genotype & phenotype; Humans; Immunohistochemistry; Immunotherapy; Lymphocyte Count; Lymphocytes; Lymphocytes, Tumor-Infiltrating - chemistry; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Medical prognosis; Metastasis; Metastatic breast cancer; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Metastasis; Pathology; PD-L1; Primary breast cancer; Rodents; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; Tissue Array Analysis; Tumor infiltrating lymphocytes; Tumor Microenvironment; Tumors; PD-L1; Metastatic breast cancer; Tumor infiltrating lymphocytes; Tumor microenvironment; Primary breast cancer
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2015.09.003

Summary Programmed 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.