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2017 ; 8
(34
): 57121-57133
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Data-driven analysis of immune infiltrate in a large cohort of breast cancer and
its association with disease progression, ER activity, and genomic complexity
#MMPMID28915659
Dannenfelser R
; Nome M
; Tahiri A
; Ursini-Siegel J
; Vollan HKM
; Haakensen VD
; Helland Å
; Naume B
; Caldas C
; Børresen-Dale AL
; Kristensen VN
; Troyanskaya OG
Oncotarget
2017[Aug]; 8
(34
): 57121-57133
PMID28915659
show ga
The tumor microenvironment is now widely recognized for its role in tumor
progression, treatment response, and clinical outcome. The intratumoral
immunological landscape, in particular, has been shown to exert both
pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active
or silent tumors may be an important indication for administration of therapy,
and detecting early infiltration patterns may uncover factors that contribute to
early risk. Thus far, direct detailed studies of the cell composition of tumor
infiltration have been limited; with some studies giving approximate
quantifications using immunohistochemistry and other small studies obtaining
detailed measurements by isolating cells from excised tumors and sorting them
using flow cytometry. Herein we utilize a machine learning based approach to
identify lymphocyte markers with which we can quantify the presence of B cells,
cytotoxic T-lymphocytes, T-helper 1, and T-helper 2 cells in any gene expression
data set and apply it to studies of breast tissue. By leveraging over 2,100
samples from existing large scale studies, we are able to find an inherent cell
heterogeneity in clinically characterized immune infiltrates, a strong link
between estrogen receptor activity and infiltration in normal and tumor tissues,
changes with genomic complexity, and identify characteristic differences in
lymphocyte expression among molecular groupings. With our extendable methodology
for capturing cell type specific signal we systematically studied immune
infiltration in breast cancer, finding an inverse correlation between beneficial
lymphocyte infiltration and estrogen receptor activity in normal breast tissue
and reduced infiltration in estrogen receptor negative tumors with high genomic
complexity.