TY - JOUR
T1 - A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer
T2 - Implications for immune-based therapies
AU - Muraro, Elena
AU - Martorelli, Debora
AU - Turchet, Elisa
AU - Miolo, Gianmaria
AU - Scalone, Simona
AU - Comaro, Elisa
AU - Talamini, Renato
AU - Mastorci, Katy
AU - Lombardi, Davide
AU - Perin, Tiziana
AU - Carbone, Antonino
AU - Veronesi, Andrea
AU - Crivellari, Diana
AU - Dolcetti, Riccardo
PY - 2011/11/23
Y1 - 2011/11/23
N2 - 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.
AB - 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.
KW - Antitumor immune responses
KW - Breast cancer
KW - Her2
KW - Neoadjuvant therapy
KW - Trastuzumab
KW - Tumor-associated antigens
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U2 - 10.1186/bcr3060
DO - 10.1186/bcr3060
M3 - Article
C2 - 22112244
AN - SCOPUS:81555232613
VL - 13
JO - Breast Cancer Research
JF - Breast Cancer Research
SN - 1465-5411
IS - 6
M1 - R117
ER -