PMID- 26183924
OWN - NLM
STAT- MEDLINE
DCOM- 20151125
LR  - 20180425
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 75
IP  - 17
DP  - 2015 Sep 1
TI  - Immunosuppressive and Prometastatic Functions of Myeloid-Derived Suppressive
      Cells Rely upon Education from Tumor-Associated B Cells.
PG  - 3456-65
LID - 10.1158/0008-5472.CAN-14-3077 [doi]
AB  - 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 TgfbetaR1/TgfbetaR2 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 TgfbetaR 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.
CI  - (c)2015 American Association for Cancer Research.
FAU - Bodogai, Monica
AU  - Bodogai M
AD  - Immune Regulation Section, Laboratory of Molecular Biology and Immunology,
      National Institute on Aging, Baltimore, Maryland.
FAU - Moritoh, Kanako
AU  - Moritoh K
AD  - Immune Regulation Section, Laboratory of Molecular Biology and Immunology,
      National Institute on Aging, Baltimore, Maryland.
FAU - Lee-Chang, Catalina
AU  - Lee-Chang C
AD  - Immune Regulation Section, Laboratory of Molecular Biology and Immunology,
      National Institute on Aging, Baltimore, Maryland.
FAU - Hollander, Christine M
AU  - Hollander CM
AD  - Tumor Microenvironment Section, Laboratory of Cancer Biology and Genetics,
      National Cancer Institute, Bethesda, Maryland.
FAU - Sherman-Baust, Cheryl A
AU  - Sherman-Baust CA
AD  - Immune Regulation Section, Laboratory of Molecular Biology and Immunology,
      National Institute on Aging, Baltimore, Maryland.
FAU - Wersto, Robert P
AU  - Wersto RP
AD  - Flow Cytometry Unit, National Institute on Aging, Baltimore, Maryland.
FAU - Araki, Yoshihiko
AU  - Araki Y
AD  - Juntendo University Graduate School of Medicine, Chiba, Japan.
FAU - Miyoshi, Ichiro
AU  - Miyoshi I
AD  - Center for Experimental Animal Science, Nagoya City University Graduate School of
      Medicine, Nagoya, Japan.
FAU - Yang, Li
AU  - Yang L
AD  - Tumor Microenvironment Section, Laboratory of Cancer Biology and Genetics,
      National Cancer Institute, Bethesda, Maryland.
FAU - Trinchieri, Giorgio
AU  - Trinchieri G
AD  - Cancer Immunobiology Section, Laboratory of Experimental Immunology, National
      Cancer Institute, Frederick, Maryland.
FAU - Biragyn, Arya
AU  - Biragyn A
AD  - Immune Regulation Section, Laboratory of Molecular Biology and Immunology,
      National Institute on Aging, Baltimore, Maryland. biragyna@mail.nih.gov.
LA  - eng
GR  - Z01 AG000443-01/NULL/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150716
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - EC 2.7.1.11 (TGF-beta type I receptor)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (transforming growth factor-beta type II receptor)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes, Regulatory/*immunology/pathology
MH  - Cell Lineage/immunology
MH  - Disease Models, Animal
MH  - Granulocytes/immunology/pathology
MH  - Humans
MH  - *Immunosuppression
MH  - Melanoma, Experimental/*immunology/pathology
MH  - Mice
MH  - Monocytes/immunology/pathology
MH  - Myeloid Cells/*immunology/pathology
MH  - Protein-Serine-Threonine Kinases/immunology/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Transforming Growth Factor beta/immunology/metabolism
MH  - Signal Transduction/immunology
PMC - PMC4558269
MID - NIHMS708309
EDAT- 2015/07/18 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/07/18 06:00
PHST- 2014/11/10 00:00 [received]
PHST- 2015/06/13 00:00 [accepted]
PHST- 2015/07/18 06:00 [entrez]
PHST- 2015/07/18 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 0008-5472.CAN-14-3077 [pii]
AID - 10.1158/0008-5472.CAN-14-3077 [doi]
PST - ppublish
SO  - Cancer Res. 2015 Sep 1;75(17):3456-65. doi: 10.1158/0008-5472.CAN-14-3077. Epub
      2015 Jul 16.