title: PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas.
abstract: 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.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287; Department of Oncology, The Johns Hopkins Hospital, Baltimore, MD 21287. Electronic address: acimino@jhmi.edu.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thompson
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287; Department of Dermatology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.affiliation: Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Oncology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Alan
authors.initials: A
authors.lastname: Meeker
authors.affiliation: Department of Dermatology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Kristen
authors.initials: K
authors.lastname: Lecksell
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Toby C
authors.initials: TC
authors.lastname: Cornish
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Nathan
authors.initials: N
authors.lastname: Cuka
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21287; Department of Oncology, The Johns Hopkins Hospital, Baltimore, MD 21287.
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.affiliation: Department of Oncology, The Johns Hopkins Hospital, Baltimore, MD 21287. Electronic address: emensle@jhmi.edu.
authors.forename: Leisha A
authors.initials: LA
authors.lastname: Emens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000737:chemistry* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016176:T-Lymphocyte Subsets / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: Metastatic breast cancer; PD-L1; Primary breast cancer; Tumor infiltrating lymphocytes; Tumor microenvironment