title: Immunosuppressive and Prometastatic Functions of Myeloid-Derived Suppressive Cells Rely upon Education from Tumor-Associated B Cells.
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 the immunosuppressive and prometastatic functions of MDSC.
authors.affiliation: Immune Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland.
authors.forename: Monica
authors.initials: M
authors.lastname: Bodogai
authors.affiliation: Immune Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland.
authors.forename: Kanako
authors.initials: K
authors.lastname: Moritoh
authors.affiliation: Immune Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland.
authors.forename: Catalina
authors.initials: C
authors.lastname: Lee-Chang
authors.affiliation: Tumor Microenvironment Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hollander
authors.affiliation: Immune Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Sherman-Baust
authors.affiliation: Flow Cytometry Unit, National Institute on Aging, Baltimore, Maryland.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Wersto
authors.affiliation: Juntendo University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Araki
authors.affiliation: Center for Experimental Animal Science, Nagoya City University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.affiliation: Tumor Microenvironment Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Cancer Immunobiology Section, Laboratory of Experimental Immunology, National Cancer Institute, Frederick, Maryland.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.affiliation: Immune Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland. biragyna@mail.nih.gov.
authors.forename: Arya
authors.initials: A
authors.lastname: Biragyn
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D019070:Cell Lineage / Q000276:immunology; D004195:Disease Models, Animal; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007165:Immunosuppression Therapy; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D017382:Reactive Oxygen Species; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II