Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development
Autor: | Erin Miller, Daniel W. Visscher, Derek C. Radisky, Muhammad Arshad, Amy C. Degnim, Jodi M. Carter, Keith L. Knutson, Lori A. Denison, Tanya L. Hoskin, Stacey J. Winham, Linda M. Murphy, Rushin A. Brahmbhatt, Alvaro Pena, Melody Stallings-Mann, Marlene H. Frost, Celine M. Vachon |
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Rok vydání: | 2017 |
Předmět: |
Adult
CD4-Positive T-Lymphocytes 0301 basic medicine Cancer Research Pathology medicine.medical_specialty CD11c Breast Neoplasms CD8-Positive T-Lymphocytes 03 medical and health sciences 0302 clinical medicine Breast cancer Immune system Antigen Risk Factors T-Lymphocyte Subsets Neoplasms Humans Medicine Breast skin and connective tissue diseases Aged CD20 B-Lymphocytes biology business.industry CD68 Macrophages Dendritic Cells Middle Aged Antigens CD20 medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Female Breast disease business Precancerous Conditions CD8 |
Zdroj: | Clinical Cancer Research. 23:3945-3952 |
ISSN: | 1557-3265 1078-0432 |
Popis: | Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD). Experimental Design: A breast tissue matched case–control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm2 for CD4+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophages and quantification of positive pixel measure for CD11c (dendritic cells). Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8+ T cells, CD11c+ dendritic cells, CD20+ B cells, and CD68+ macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20+ cell density (P = 0.04). Nearly 42% of BBD cases had no CD20+ B cells in evaluated lobules compared with 28% of BBD controls (P = 0.02). The absence of CD20+ cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4–23.1) for subsequent breast cancer risk. Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945–52. ©2017 AACR. |
Databáze: | OpenAIRE |
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