title: The immune microenvironment of breast ductal carcinoma in situ.
abstract: The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1-tumor infiltrating lymphocytes were seen only in ER+/HER-2-DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thompson
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.|Department of Pathology and Dermatology, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Elwood
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Meeker
authors.affiliation: Department of Pathology, University of Tuebingen, Tuebingen, Baden-Wurttenberg, Germany.
authors.forename: Hind Nassar
authors.initials: HN
authors.lastname: Warzecha
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.|Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.|Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
authors.affiliation: Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Leisha A
authors.initials: LA
authors.lastname: Emens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000276:immunology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor