Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer

Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters....

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Main Authors: Mohsen Arabpour, Atri Ghods, Mahmoud Shariat, Abodl-Rasoul Talei, Fereshteh Mehdipour, Abbas Ghaderi
Format: Article
Language:English
Published: Shiraz University of Medical Sciences 2019-06-01
Series:Iranian Journal of Immunology
Subjects:
Online Access:https://iji.sums.ac.ir/article_44936_48e319be3c4123ffac7dbc073a56508d.pdf
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author Mohsen Arabpour
Atri Ghods
Mahmoud Shariat
Abodl-Rasoul Talei
Fereshteh Mehdipour
Abbas Ghaderi
author_facet Mohsen Arabpour
Atri Ghods
Mahmoud Shariat
Abodl-Rasoul Talei
Fereshteh Mehdipour
Abbas Ghaderi
author_sort Mohsen Arabpour
collection DOAJ
description Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry. Results: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage. Conclusions: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.
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spelling doaj.art-09480d6b4e634698acbb3ce98f5d4cb72022-12-21T20:01:05ZengShiraz University of Medical SciencesIranian Journal of Immunology1735-13831735-367X2019-06-0116210811610.22034/iji.2019.8025444936Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast CancerMohsen Arabpour0Atri Ghods1Mahmoud Shariat2Abodl-Rasoul Talei3Fereshteh Mehdipour4Abbas Ghaderi5Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Pathology, Shiraz Central Hospital, Shiraz, IranBreast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, IranShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranBackground: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry. Results: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage. Conclusions: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.https://iji.sums.ac.ir/article_44936_48e319be3c4123ffac7dbc073a56508d.pdf4-1bblbreast cancerb cellstumor draining lymph nodes
spellingShingle Mohsen Arabpour
Atri Ghods
Mahmoud Shariat
Abodl-Rasoul Talei
Fereshteh Mehdipour
Abbas Ghaderi
Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer
Iranian Journal of Immunology
4-1bbl
breast cancer
b cells
tumor draining lymph nodes
title Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer
title_full Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer
title_fullStr Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer
title_full_unstemmed Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer
title_short Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer
title_sort correlation of 4 1bbl b cells in tumor draining lymph nodes with pathological characteristics of breast cancer
topic 4-1bbl
breast cancer
b cells
tumor draining lymph nodes
url https://iji.sums.ac.ir/article_44936_48e319be3c4123ffac7dbc073a56508d.pdf
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