The immune microenvironment of breast ductal carcinoma in situ

Elizabeth Thompson, Janis M Taube, Hillary Elwood, Rajni Sharma, Alan Keith Meeker, Hind Nassar Warzecha, Pedram Argani, Ashley M Cimino-Mathews, Leisha A. Emens

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)249-258
Number of pages10
JournalModern Pathology
Volume29
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Tumor-Infiltrating Lymphocytes
Ligands
Breast Neoplasms
Epidermal Growth Factor
Estrogen Receptors
Breast Carcinoma In Situ
Ductal Carcinoma
Progesterone Receptors
Immunohistochemistry
Lymphocytes
Carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

The immune microenvironment of breast ductal carcinoma in situ. / Thompson, Elizabeth; Taube, Janis M; Elwood, Hillary; Sharma, Rajni; Meeker, Alan Keith; Warzecha, Hind Nassar; Argani, Pedram; Cimino-Mathews, Ashley M; Emens, Leisha A.

In: Modern Pathology, Vol. 29, No. 3, 01.03.2016, p. 249-258.

Research output: Contribution to journalArticle

Thompson, Elizabeth ; Taube, Janis M ; Elwood, Hillary ; Sharma, Rajni ; Meeker, Alan Keith ; Warzecha, Hind Nassar ; Argani, Pedram ; Cimino-Mathews, Ashley M ; Emens, Leisha A. / The immune microenvironment of breast ductal carcinoma in situ. In: Modern Pathology. 2016 ; Vol. 29, No. 3. pp. 249-258.
@article{14c2d58136cc499fb78b6b8f3a71ec60,
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.",
author = "Elizabeth Thompson and Taube, {Janis M} and Hillary Elwood and Rajni Sharma and Meeker, {Alan Keith} and Warzecha, {Hind Nassar} and Pedram Argani and Cimino-Mathews, {Ashley M} and Emens, {Leisha A.}",
year = "2016",
month = "3",
day = "1",
doi = "10.1038/modpathol.2015.158",
language = "English (US)",
volume = "29",
pages = "249--258",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - The immune microenvironment of breast ductal carcinoma in situ

AU - Thompson, Elizabeth

AU - Taube, Janis M

AU - Elwood, Hillary

AU - Sharma, Rajni

AU - Meeker, Alan Keith

AU - Warzecha, Hind Nassar

AU - Argani, Pedram

AU - Cimino-Mathews, Ashley M

AU - Emens, Leisha A.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84959466395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959466395&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2015.158

DO - 10.1038/modpathol.2015.158

M3 - Article

C2 - 26769139

AN - SCOPUS:84959466395

VL - 29

SP - 249

EP - 258

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 3

ER -