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Breast Cancer Research
Published in: Breast Cancer Research 6/2011

Open Access 01-12-2011 | Research article

A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies

Authors: Elena Muraro, Debora Martorelli, Elisa Turchet, Gianmaria Miolo, Simona Scalone, Elisa Comaro, Renato Talamini, Katy Mastorci, Davide Lombardi, Tiziana Perin, Antonino Carbone, Andrea Veronesi, Diana Crivellari, Riccardo Dolcetti

Published in: Breast Cancer Research | Issue 6/2011

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Abstract

Introduction

The clinical efficacy of trastuzumab and taxanes is at least partly related to their ability to mediate or promote antitumor immune responses. On these grounds, a careful analysis of basal immune profile may be capital to dissect the heterogeneity of clinical responses to these drugs in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.

Methods

Blood samples were collected from 61 locally advanced breast cancers (36 HER2- and 25 HER2+) at diagnosis and from 23 healthy women. Immunophenotypic profiling of circulating and intratumor immune cells, including regulatory T (Treg) cells, was assessed by flow cytometry and immunohistochemistry, respectively. Serum levels of 10 different cytokines were assessed by multiplex immunoassays. CD8+ T cell responses to multiple tumor-associated antigens (TAA) were evaluated by IFN-γ-enzyme-linked immunosorbent spot (ELISPOT). The Student's t test for two tailed distributions and the Wilcoxon two-sample test were used for the statistical analysis of the data.

Results

The proportion of circulating immune effectors was similar in HER2+ patients and healthy donors, whereas higher percentages of natural killer and Treg cells and a lower CD4+/CD8+ T cell ratio (with a prevalence of naïve and central memory CD8+ T cells) were observed in HER2- cases. Higher numbers of circulating CD8+ T cells specific for several HLA-A*0201-restricted TAA-derived peptides were observed in HER2+ cases, together with a higher prevalence of intratumor CD8+ T cells. Serum cytokine profile of HER2+ patients was similar to that of controls, whereas HER2- cases showed significantly lower cytokine amounts compared to healthy women (IL-2, IL-8, IL-6) and HER2+ cases (IL-2, IL-1β, IL-8, IL-6, IL-10).

Conclusions

Compared to HER2- cases, patients with HER2-overexpressing locally advanced breast cancer show a more limited tumor-related immune suppression. This may account for the clinical benefit achieved in this subset of patients with the use of drugs acting through, but also promoting, immune-mediated effects.
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Metadata
Title
A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies
Authors
Elena Muraro
Debora Martorelli
Elisa Turchet
Gianmaria Miolo
Simona Scalone
Elisa Comaro
Renato Talamini
Katy Mastorci
Davide Lombardi
Tiziana Perin
Antonino Carbone
Andrea Veronesi
Diana Crivellari
Riccardo Dolcetti
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3060

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