Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells

Monica Bodogai, Kanako Moritoh, Catalina Lee Chang, Christine M. Hollander, Cheryl A. Sherman-Baust, Robert P. Wersto, Yoshihiko Araki, Ichiro Miyoshi, Li Yang, Giorgio Trinchieri, Arya Biragyn*

*Corresponding author for this work

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Myeloid-derived suppressive cells (MDSC) have been reported to promote metastasis, but the loss of cancer-induced B cells/B regulatory cells (tBreg) can block metastasis despite MDSC expansion in cancer. Here, using multiple murine tumor models and human MDSC, we show that MDSC populations that expand in cancer have only partially primed regulatory function and limited prometastatic activity unless they are fully educated by tBregs. Cancer-induced tBregs directly activate the regulatory function of both the monocyte and granulocyte subpopulations of MDSC, relying, in part, on TgfβR1/TgfβR2 signaling.MDSC fully educated in this manner exhibit an increased production of reactive oxygen species and NO and more efficiently suppress CD4+ and CD8+ T cells, thereby promoting tumor growth and metastasis. Thus, loss of tBregs or TgfβR deficiency in MDSC is sufficient to disable their suppressive function and to block metastasis. Overall, our data indicate that cancer-induced B cells/B regulatory cells are important regulators of theimmunosuppressive and prometastatic functions of MDSC.

Original languageEnglish (US)
Pages (from-to)3456-3465
Number of pages10
JournalCancer Research
Volume75
Issue number17
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Bodogai, M., Moritoh, K., Lee Chang, C., Hollander, C. M., Sherman-Baust, C. A., Wersto, R. P., Araki, Y., Miyoshi, I., Yang, L., Trinchieri, G., & Biragyn, A. (2015). Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells. Cancer Research, 75(17), 3456-3465. https://doi.org/10.1158/0008-5472.CAN-14-3077