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| Home > Institute Collections > W500 > Tumor-Associated Neutrophils Drive B-cell Recruitment and Their Differentiation to Plasma Cells. |
| Home > Institute Collections > W500 > Tumor-Associated Neutrophils Drive B-cell Recruitment and Their Differentiation to Plasma Cells. |
| Journal Article | DKFZ-2025-02410 |
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2021
AACR
Philadelphia, Pa.
Abstract: A major mechanism through which neutrophils have been suggested to modulate tumor progression involves the interaction and subsequent modulation of other infiltrating immune cells. B cells have been found to infiltrate various cancer types and play a role in tumor immunity, offering new immunotherapy opportunities. Nevertheless, the specific impact of tumor-associated neutrophils (TAN) on B cells has largely been overlooked. In the current study, we aimed to characterize the role of TANs in the recruitment and modulation of B cells in the tumor microenvironment (TME). We showed that TANs actively participate in the recruitment of B cells to the TME and identified TNFα as the major cytokine mediating B-cell chemotaxis by TANs. The recruitment of CD45+B220+CD138- splenic B cells by TANs in vitro resulted in B-cell phenotypic modulation, with 68.6% ± 2.1% of the total migrated B cells displaying a CD45-B220+CD138+ phenotype, which is typical for plasma cells. This phenotype mirrored the large proportion (54.0% ± 6.1%) of CD45-B220+CD138+ intratumoral B cells (i.e., plasma cells) in Lewis lung carcinoma tumors. We next confirmed that the differentiation of CD45+B220+CD138- B cells to functionally active CD45-B220+CD138+ plasma cells required contact with TANs, was independent of T cells, and resulted in IgG production. We further identified membranal B-cell activating factor (BAFF) on TANs as a potential contact mechanism mediating B-cell differentiation, as blocking BAFF-receptor (BAFF-R) significantly reduced IgG production by 20%. Our study, therefore, demonstrates that TANs drive the recruitment and modulation of B cells into plasma cells in the TME, hence opening new avenues in the targeting of the immune system in cancer.
Keyword(s): Animals (MeSH) ; B-Cell Activating Factor: metabolism (MeSH) ; B-Cell Activation Factor Receptor: antagonists & inhibitors (MeSH) ; B-Cell Activation Factor Receptor: metabolism (MeSH) ; Breast Neoplasms: immunology (MeSH) ; Breast Neoplasms: pathology (MeSH) ; Carcinoma, Lewis Lung: immunology (MeSH) ; Carcinoma, Lewis Lung: pathology (MeSH) ; Cell Differentiation: immunology (MeSH) ; Cell Line, Tumor (MeSH) ; Chemotaxis, Leukocyte: immunology (MeSH) ; Disease Models, Animal (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Lymphocyte Activation (MeSH) ; Mice (MeSH) ; Neutrophils: immunology (MeSH) ; Neutrophils: metabolism (MeSH) ; Plasma Cells: immunology (MeSH) ; Plasma Cells: metabolism (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Tumor Necrosis Factor-alpha: metabolism (MeSH) ; B-Cell Activating Factor ; B-Cell Activation Factor Receptor ; Tnf protein, mouse ; Tnfrsf13c protein, mouse ; Tnfsf13b protein, mouse ; Tumor Necrosis Factor-alpha
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