Fereshteh Mehdipour1, Mahboobeh Razmkhah1, Zahra Faghih1, Mandana Bagheri2, Abdol-Rasoul Talei3, Abbas Ghaderi4,5. 1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-3119, Shiraz, Iran. 2. Department of Pathology, Shiraz Central Hospital, Shiraz, Iran. 3. Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 4. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-3119, Shiraz, Iran. ghaderia@sums.ac.ir. 5. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. ghaderia@sums.ac.ir.
Abstract
PURPOSE: The role of cytokine-producing B cells in antitumor immunity is mostly overlooked. In the present study, we investigated changes in B cell cytokine profiles in breast tumor-draining lymph nodes (TDLNs) during disease progression, and associations of these changes with prognostic indicators. METHODS: Flow cytometry was used to measure the expression of TNF-α, IL-10, TGF-β, IL-2 and IFN-γ in B cells from 42 axillary lymph nodes. The frequencies of IL-10+ and FoxP3+ T regulatory cells (Tregs) were also determined. RESULTS: No significant changes in B cell cytokine profiles were observed during breast cancer progression from stage I to III, but the percentage of B cells with high TNF-α expression (TNFhi) showed a negative relationship with lymph node involvement and Her2 expression (p < 0.05). The percentage of IL-10+ B cells was found to be significantly higher in non-metastatic lymph nodes in node-negative compared to node-positive patients (p = 0.001). The frequencies of IL-10+ and TNFhi B cells were found to be negatively correlated with the number of involved lymph nodes. The frequency of TNFhi B cells showed an inverse correlation with the frequency of FoxP3+ Tregs, which in turn was associated with indicators of a poor prognosis. CONCLUSIONS: Our data indicate that the cytokine profiles of B cells in TDLNs of patients with breast cancer show associations with various disease parameters. TNFhi and IL-10+ B cells correlated positively with indicators of a good prognosis. Further functional studies are required to elucidate the role of cytokine production by B cells in immunity against breast cancer.
PURPOSE: The role of cytokine-producing B cells in antitumor immunity is mostly overlooked. In the present study, we investigated changes in B cell cytokine profiles in breast tumor-draining lymph nodes (TDLNs) during disease progression, and associations of these changes with prognostic indicators. METHODS: Flow cytometry was used to measure the expression of TNF-α, IL-10, TGF-β, IL-2 and IFN-γ in B cells from 42 axillary lymph nodes. The frequencies of IL-10+ and FoxP3+ T regulatory cells (Tregs) were also determined. RESULTS: No significant changes in B cell cytokine profiles were observed during breast cancer progression from stage I to III, but the percentage of B cells with high TNF-α expression (TNFhi) showed a negative relationship with lymph node involvement and Her2 expression (p < 0.05). The percentage of IL-10+ B cells was found to be significantly higher in non-metastatic lymph nodes in node-negative compared to node-positive patients (p = 0.001). The frequencies of IL-10+ and TNFhi B cells were found to be negatively correlated with the number of involved lymph nodes. The frequency of TNFhi B cells showed an inverse correlation with the frequency of FoxP3+ Tregs, which in turn was associated with indicators of a poor prognosis. CONCLUSIONS: Our data indicate that the cytokine profiles of B cells in TDLNs of patients with breast cancer show associations with various disease parameters. TNFhi and IL-10+ B cells correlated positively with indicators of a good prognosis. Further functional studies are required to elucidate the role of cytokine production by B cells in immunity against breast cancer.
Entities:
Keywords:
B cells; B10 cells; Breast cancer; T regulatory cells; TNF-α; Tumor-draining lymph nodes
Authors: Holbrook E Kohrt; Navid Nouri; Kent Nowels; Denise Johnson; Susan Holmes; Peter P Lee Journal: PLoS Med Date: 2005-09-06 Impact factor: 11.069
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