Unknown

Dataset Information

0

Ascites-derived IL-6 and IL-10 synergistically expand CD14+HLA-DR-/low myeloid-derived suppressor cells in ovarian cancer patients.


ABSTRACT: Myeloid-derived suppressor cells (MDSC) play a key immunosuppressive role in various types of cancer, including ovarian cancer (OC). In this study, we characterized CD14+HLA-DR-/lo MDSC with a typical monocytic phenotype (M-MDSC) in the peripheral blood (PB) and ascites from OC patients. Compared to healthy donors, OC patients had a significantly increased abundance of M-MDSC in both PB and ascites; importantly, their abundance in both compartments was inversely associated with the prognosis where OC patients with higher level of M-MDSC having a shorter relapse-free survival. Intriguingly, we demonstrated that M-MDSC could be readily induced by ascitic fluids (AF) from OC patients, which was predominantly dependent on IL-6, IL-10 and STAT3 activation as neutralization of IL-6 and/or IL-10 or inhibition of STAT3 abrogated MDSC's expansion while recombinant IL-6 and IL-10 recapitulated the expansive effect of AF; furthermore, predominantly elevated levels of IL-6 and IL-10 has been noted in the AF which was positively correlated with the abundance of M-MDSC as well as poor prognosis of OC patients. As expected, we observed that AF-driven STAT3 activation upregulated the expression of arginase (ARG1) and inducible nitric oxide synthase (iNOS) in induced M-MDSC through which these MDSC executed the immunosuppressive activity. Taken together, these results demonstrate that abundant M-MDSC are present in both periphery and ascites of OC patients whose accumulation and suppressive activity is critically attributable to ascites-derived IL-6 and IL-10 and their downstream STAT3 signal, thus providing a potentially novel therapeutic option by locally targeting MDSC to improve antitumor efficacy.

SUBMITTER: Wu L 

PROVIDER: S-EPMC5652747 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Ascites-derived IL-6 and IL-10 synergistically expand CD14<sup>+</sup>HLA-DR<sup>-/low</sup> myeloid-derived suppressor cells in ovarian cancer patients.

Wu Liangliang L   Deng Zhaoyang Z   Peng Yaojun Y   Han Lu L   Liu Jing J   Wang Linxiong L   Li Bohua B   Zhao Jian J   Jiao Shunchang S   Wei Huafeng H  

Oncotarget 20170810 44


Myeloid-derived suppressor cells (MDSC) play a key immunosuppressive role in various types of cancer, including ovarian cancer (OC). In this study, we characterized CD14<sup>+</sup>HLA-DR<sup>-/lo</sup> MDSC with a typical monocytic phenotype (M-MDSC) in the peripheral blood (PB) and ascites from OC patients. Compared to healthy donors, OC patients had a significantly increased abundance of M-MDSC in both PB and ascites; importantly, their abundance in both compartments was inversely associated  ...[more]

Similar Datasets

| S-EPMC5494936 | biostudies-other
2011-09-08 | E-GEOD-32001 | biostudies-arrayexpress
2011-09-09 | GSE32001 | GEO
| S-EPMC7180989 | biostudies-literature
| S-EPMC3035079 | biostudies-other
| S-EPMC4485750 | biostudies-literature
| S-EPMC6250615 | biostudies-literature
| S-EPMC3954539 | biostudies-literature
| S-EPMC3701116 | biostudies-literature
| S-EPMC3549558 | biostudies-literature