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

Muraro, Elena, Martorelli, Debora, Turchet, Elisa, Miolo, Gianmaria, Scalone, Simona, Comaro, Elisa, Talamini, Renato, Mastorci, Katy, Lombardi, Davide, Perin, Tiziana, Carbone, Antonino, Veronesi, Andrea, Crivellari, Diana and Dolcetti, Riccardo (2011) A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies. Breast Cancer Research, 13 . doi:10.1186/bcr3060


Author Muraro, Elena
Martorelli, Debora
Turchet, Elisa
Miolo, Gianmaria
Scalone, Simona
Comaro, Elisa
Talamini, Renato
Mastorci, Katy
Lombardi, Davide
Perin, Tiziana
Carbone, Antonino
Veronesi, Andrea
Crivellari, Diana
Dolcetti, Riccardo
Title A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies
Journal name Breast Cancer Research   Check publisher's open access policy
ISSN 1465-5411
1465-542X
Publication date 2011-11-23
Year available 2011
Sub-type Article (original research)
DOI 10.1186/bcr3060
Open Access Status DOI
Volume 13
Total pages 13
Place of publication London, United Kingdom
Publisher Current Medicine Group
Language eng
Formatted 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.
Keyword Antitumor immune responses
Breast cancer
Her2
Neoadjuvant therapy
Trastuzumab
Tumor-associated antigens
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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