Tumor-associated neutrophils drive b-cell recruitment and their differentiation to plasma cells

Merav E. Shaul, Asaf Zlotnik, Einat Tidhar, Asaf Schwartz, Ludovica Arpinati, Naomi Kaisar-Iluz, Sojod Mahroum, Inbal Mishalian, Zvi G. Fridlender*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 TNFa as the major cytokine mediating B-cell chemotaxis by TANs. The recruitment of CD45 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 phenotype, which is typical for plasma cells. This phenotype mirrored the large proportion (54.0% ± 6.1%) of CD45-B220 intratumoral B cells (i.e., plasma cells) in Lewis lung carcinoma tumors. We next confirmed that the differentiation of CD45 B cells to functionally active CD45-B220 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.

Original languageAmerican English
Pages (from-to)811-824
Number of pages14
JournalCancer Immunology Research
Volume9
Issue number7
DOIs
StatePublished - Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 American Association for Cancer Research.

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