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

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.

• Publication year

  2017

• Venue

  OncoTarget

• Publication date

  2017-08-10

• Fields of study

  Medicine

• Identifiers
  DOI 10.18632/oncotarget.20164PMID 29100353PMCID 5652747
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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