Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.

Abstract:

:To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2+ breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

journal_name

Cancer Discov

journal_title

Cancer discovery

authors

Gil Del Alcazar CR,Huh SJ,Ekram MB,Trinh A,Liu LL,Beca F,Zi X,Kwak M,Bergholtz H,Su Y,Ding L,Russnes HG,Richardson AL,Babski K,Min Hui Kim E,McDonnell CH 3rd,Wagner J,Rowberry R,Freeman GJ,Dillon D,Sorlie T,Cous

doi

10.1158/2159-8290.CD-17-0222

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

1098-1115

issue

10

eissn

2159-8274

issn

2159-8290

pii

2159-8290.CD-17-0222

journal_volume

7

pub_type

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