Impact of Epithelial–Mesenchymal Transition on the Immune Landscape in Breast Cancer

Abstract

The impact of epithelial–mesenchymal transition (EMT) signature on the immune infiltrate present in the breast cancer tumor microenvironment (TME) is still poorly understood. Since there is mounting interest in the use of immunotherapy for the treatment of subsets of breast cancer patients, it is of major importance to understand the fundamental tumor characteristics which dictate the inter-tumor heterogeneity in immune landscapes. We aimed to assess the impact of EMT-related markers on the nature and magnitude of the inflammatory infiltrate present in breast cancer TME and their association with the clinicopathological parameters. Tissue microarrays were constructed from 144 formalin-fixed paraffin-embedded invasive breast cancer tumor samples. The protein expression patterns of Snail, Twist, ZEB1, N-cadherin, Vimentin, GRHL2, E-cadherin, and EpCAM were examined by immunohistochemistry (IHC). The inflammatory infiltrate in the TME was assessed semi-quantitatively on hematoxylin and eosin (H&E)-stained whole sections and was characterized using IHC. The inflammatory infiltrate was more intense in poorly differentiated carcinomas and triple-negative carcinomas in which the expression of E-cadherin and GRHL2 was reduced, while EpCAM was overexpressed. Most EMT-related markers correlated with plasma cell infiltration of the TME. Taken together, our findings reveal that the EMT signature might impact the immune response in the TME.

Immune Checkpoint Blockade Therapy for Breast Cancer: Lessons from Epithelial–Mesenchymal Transition

“…In contrast, epithelial states were largely dominant in the luminal A subtype [ 51 ]. Along similar lines, two other studies revealed that the mesenchymal markers N-cadherin and vimentin positively correlated with a higher histological grade and the absence of hormone receptors in breast tumors [ 52 , 53 ]. Thus, a loss of E-cadherin and gain of N-cadherin and vimentin has been reported in TNBCs, invasive lobular carcinomas and a subset of invasive ductal carcinomas [ 52 , 53 ].…”

“…Importantly, many of these immune regulatory factors that are expressed by cancer cells undergoing an EMT are also indicative of poor prognosis of TNBCs. Moreover, a subset of TNBCs themselves, activate components of the EMT program [ 51 , 52 ]. This striking overlap of immune-regulatory factors that are expressed by cancer cells undergoing an EMT and by TNBC tumors, brings to the forefront the attractive possibility of using the EMT program as a parameter that can be (1) used as a predictive criterion for responses of breast tumors to immunotherapies and (2) intercepted to potentiate the susceptibility of breast tumors to immunotherapies.…”

Ropivacaine with intraspinal administration alleviates preeclampsia-induced kidney injury via glycocalyx /alpha 7 nicotinic acetylcholine receptor pathway

“…Paraffin sections were dewaxed to water, antigenic repaired, endogenous peroxidase blocked, bovine serum albumin sealed and then co-cultured with primary antibody followed by incubation with secondary antibody [ 20 ]. DAB was used to color the slices and hematoxylin was used to re-stain the nuclei.…”

CAXII Is a Surrogate Marker for Luminal Breast Tumors Regulated by ER and GATA3

“…Tissue micro-arrays (TMAs) were prepared from cores (1 mm) extracted from each of 118 formalin-fixed and paraffin-embedded (FFPE) breast tumor tissues as previously described [ 53 ]. These samples were obtained from patients with primary breast tumors who underwent surgery at the Hôtel Dieu Hospital and at the Centre Hospitalier de l’Université de Montréal (CHUM) between 2001 and 2018.…”