Inhibition of Tumor-Derived Prostaglandin-E2 Blocks the Induction of Myeloid-Derived Suppressor Cells and Recovers Natural Killer Cell Activity

Abstract

Purpose: Increased frequencies of myeloid-derived suppressor cells (MDSC) correlate with poor prognosis in patients with cancers. Tumor-derived prostaglandin-E2 (PGE2) plays an important role in inducing MDSCs. However, the detailed mechanisms of this induction remain unknown. To develop targeted therapies for MDSCs, we sought to investigate the molecular basis of PGE2-regulated accumulation of MDSCs and their functional consequence on natural killer (NK) cell activity.Experimental Design: The effects of PGE2 in inducing phenotypic, signaling, and functional alternations on monocytes were analyzed in vitro. Suppression of NK-cell activity by PGE2-treated monocytes was compared with that of freshly isolated CD14

Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells

“…These data are concordant with pre-clinical results that showed that MDSCs mediate potent inhibition of conventional NK cells. [28, 29] In addition, increased numbers of MDSC has been detected in patients with diffuse large B cell lymphoma at diagnosis and correlated with worse outcomes. [30, 31] Furthermore tumor infiltrating MDSC have been recognized to recruit Treg cells and be permissive of further tumor growth.…”

Platelet-to-Lymphocyte Ratio and Use of NSAIDs during the Perioperative Period as Prognostic Indicators in Patients with NSCLC Undergoing Surgery

“…27 Platelets can also release growth factors, such as prostaglandin E, vascular endothelial growth factor, and transforming growth factor that disrupt the function of natural killer cells and stimulate the growth of cancer cells. 27,28 Absolute or relative lymphopenia is another important component of a high platelet-to-lymphocyte ratio in patients with NSCLC. The results from a previous study indicated that patients with low lymphocyte nadirs undergoing radiotherapy have lower rates of survival than patients whose lymphocyte levels are higher.…”

IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells

“…16 Fluorescently labeled cells were acquired in a BD LSRII flow cytometer and analyzed by FlowJo software (TreeStar; see supplemental Methods).…”