Data from Immune Escape in Breast Cancer During <i>In Situ</i> to Invasive Carcinoma Transition

Abstract

<div>Abstract<p>To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma <i>in situ</i> (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<sup>+</sup>CD3<sup>+</sup> T cells demonstrated a decrease in CD8<sup>+</sup> signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB<sup>+</sup>CD8<sup>+</sup> 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 <i>CD274</i> (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with <i>ERBB2</i> subdivided HER2<sup>+</sup> breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.</p><p><b>Significance:</b> 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 <i>in situ</i> to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. <i>Cancer Discov; 7(10); 1098–115. ©2017 AACR.</i></p><p><i>See related commentary by Speiser and Verdeil, p. 1062</i>.</p><p><i>This article is highlighted in the In This Issue feature, p. 1047</i></p></div>