Immune Profile of Inflammatory Breast Cancer Patients.

Abstract

Abstract Background: Inflammatory breast cancer (IBC) is characterized by an acute inflammation of the skin of the affected breast due to blockage of the dermal lymphatics by tumor emboli. Cytokines and chemokines affect the migration of tumor cells and immune cell function that regulates the pathogenesis of IBC. Preliminary data suggest that sera of IBC patients contain several inflammatory cytokines and chemokines capable of regulating innate and adaptive cellular immune responses. Since there is a paucity of data on the characteristics and function of immune cells of IBC patients, we determined the immunophenotype and cytokine production by T cells and dendritic cells.Methods: From October 2008 through May 2009, peripheral blood (PB) from 34 IBC patients (18 non-metastatic and 16 metastatic), 18 non-IBC patients and 24 healthy donors (HD) were analyzed to determine the immunophenotype of T-cell subsets, activated and regulatory T-cells, B-cells, natural killer cell subsets (NKC), and dendritic cell (DC) subsets. Additionally, we assessed the ability of T-cells and DCs to synthesize cytokines following activation through the T-cell receptor (TCR) and toll-like receptors (TLR), respectively. The Kruskal-Wallis and Mann-Whitney U tests determined the differences between IBC patients, non-IBC patients, and HD.Results: IBC and non-IBC patients were well-matched in terms of ER, PR, Her2, high-grade tumor, tumor size, and menopause status. Both IBC and non-IBC patients had significantly fewer lymphocytes, total T-cells (CD3+), T-helper (CD4+), T-cytotoxic/suppressor (CD8+), and B (CD19+) than HD (all p < 0.01). Non-IBC patients had a significantly lower CD4/CD8 ratio than HD (p = 0.016) while IBC patients had significantly fewer T-regulatory (CD4+CD25hiCD127-) cells than HD (p = 0.02) and non-IBC patients (p < 0.05). With respect to innate immunity markers, IBC patients also had significantly lower percentages of ADCC/NK (CD16+CD56+, p = 0.034) and non-exhaustive NK (CD56+CD57+, p = 0.02) than HD and a significantly higher percentage of non-ADCC/NK cells than non-IBC patients (p = 0.03). Non-IBC patients and HD had similar innate immunity markers. Even though all groups had similar percentages of myeloid (mDC) and plasmacytoid (pDC) dendritic cells, mDC of IBC patients displayed a higher level of constitutive activation than non-IBC with increased expression of CD40 and CD80, and decreased CCR5 expression. IBC patients had more mDC that constitutively produced TNF-a (p 0.041) and IL-10 (p = 0.029) than HD, and more mDC than non-IBC patients that produced IL-10 (p = 0.028).Conclusion: The immune profile of patients with breast cancer suggests multiple abnormalities involving T-, B-, NK- and dendritic cells. Furthermore, IBC patients exhibited constitutive immune activation as measured by increased expression of co-stimulatory receptors (CD80, CD40) and constitutive production of TNF-a and IL-10 by mDC as well as fewer T-regulatory cells. Taken together, these preliminary data suggest that IBC patients are more likely than non-IBC patients to have a dysregulated immune function. Additional studies on T-cell activation and function are warranted to better understand factors associated with host defense mechanisms of IBC patients and possible therapeutic strategies to restore immune function. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4129.