Prostaglandin E2 receptor activity and susceptibility to natural killer cells

“…16 It was demonstrated that tumor cells derived from many experimental and clinical cancers actively synthesize eicosanoids. [17][18][19] The reason for the lower serum cholesterol levels in BCC than in AK may be due to the increased absorption and utilization of cholesterol by malignant tissue than by precancerous lesions.…”

Section: Discussionmentioning

confidence: 99%

Lipid profile in actinic keratosis and basal cell carcinoma

et al. 1999

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“…The general idea is that NK cells could reject human tumors, influencing clinical outcome. In 1992, Fulton et al have firstly evaluated that PGE2 receptor, without distinguishing the isoform, is overexpressed in metastatic murine mammary tumor, and PGE2 itself is able to induce NK activity inhibition [188]. Of note, NK cells express EP2, EP3, and EP4, but not EP1 [189].…”

Section: Pge2 and Nk Activitymentioning

confidence: 99%

Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity

Finetti

Travelli

Ercoli

et al. 2020

Biology

157

146

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The involvement of inflammation in cancer progression has been the subject of research for many years. Inflammatory milieu and immune response are associated with cancer progression and recurrence. In different types of tumors, growth and metastatic phenotype characterized by the epithelial mesenchymal transition (EMT) process, stemness, and angiogenesis, are increasingly associated with intrinsic or extrinsic inflammation. Among the inflammatory mediators, prostaglandin E2 (PGE2) supports epithelial tumor aggressiveness by several mechanisms, including growth promotion, escape from apoptosis, transactivation of tyrosine kinase growth factor receptors, and induction of angiogenesis. Moreover, PGE2 is an important player in the tumor microenvironment, where it suppresses antitumor immunity and regulates tumor immune evasion, leading to increased tumoral progression. In this review, we describe the current knowledge on the pro-tumoral activity of PGE2 focusing on its role in cancer progression and in the regulation of the tumor microenvironment.

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“…Similar data have been reported previously. 37 To evaluate the effect of PGE2 on IFN-␥ production, a second NK-cell effector function, NK cells were stimulated with PMA and ionomycin in the presence or absence of different concentrations of PGE2, and the 16-hour supernatant was evaluated by ELISA for the presence of IFN-␥ production. PGE2 dose-dependently inhibited IFN-␥ secretion ( Figure 1C).…”

Section: Pge2 Directly Inhibits Nk-cell Cytokine Production and Nk Cementioning

confidence: 99%

Inflammation restraining effects of prostaglandin E2 on natural killer–dendritic cell (NK-DC) interaction are imprinted during DC maturation

Elssen

Vanderlocht

Oth

et al. 2011

Blood

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Among prostaglandins (PGs), PGE2 is abundantly expressed in various malignancies and is probably one of many factors promoting tumor growth by inhibiting tumor immune surveillance . In the current study, we report on a novel mechanism by which PGE2 inhibits in vitro natural killer-dendritic cell (NK-DC) crosstalk and thereby innate and adaptive immune responses via its effect on NK-DC crosstalk. The presence of PGE2 during IFN-␥/membrane fraction of Klebsiella pneumoniae DC maturation inhibits the production of chemokines (CCL5, CCL19, and CXCL10) and cytokines (IL-12 and IL-18), which is cAMP-dependent and imprinted during DC maturation. As a consequence, these DCs fail to attract NK cells and show a decreased capacity to trigger NK cell IFN-␥ production, which in turn leads to reduced T-helper 1 polarization. In addition, the presence of PGE2 during DC maturation impairs DC-mediated augmentation of NK-cell cytotoxicity. Op- IntroductionProstaglandins (PGs) are potent immune modulators that are produced during inflammation after the conversion of arachidonic acid by cyclooxygenase (COX). 1 Furthermore, PGs are also abundantly produced by various types of tumors. 2 COX2 expression, which is correlated with a poor prognosis, is induced in a variety of human premalignant and malignant tumors, including solid tumors as well as hematologic malignancies. [3][4][5][6] Several lines of evidence demonstrate that COX2-derived PGs are involved in the promotion of tumor growth by regulation of cancer cell proliferation, apoptosis, migration, and invasion. [7][8][9][10][11] PGs are also produced by tumor-surrounding cells, creating a tumor-supporting environment by enhancing angiogenesis and inhibiting tumor immune surveillance. 2,[11][12][13][14] Of all prostaglandins, PGE2 has a pivotal role in tumor immunosuppression. It has been hypothesized that this effect is caused by induction of a permanent state of inflammation, 2 resulting in phenotypic and functional changes of T-helper (T H ) cells, cytotoxic T-lymphocyte (CTL) cells, dendritic cells (DCs), natural killer (NK) cells, and myeloid-derived suppressor cells. 12 PGE2 has been shown to deviate T H cell skewing from an antitumor T H 1 response toward a T H 2/T H 17 response by direct binding to these cells. [15][16][17] In addition, PGE2 is responsible for shifting the balance of IL-12/IL-23 production by DCs toward IL-23, which is a very potent cytokine responsible for T H 17 expansion and survival. 18,19 As a consequence, less IL-12 and other proinflammatory cytokines are produced, thereby inhibiting T H 1 polarization. 17,20 PGE2 also decreases the cytotoxic capacity of CTLs directly by inducing the expression of inhibitory receptors on CTLs 21 and indirectly by inhibiting DC maturation and antigen presentation. 22,23 Moreover, tumor-associated PGE2 has been reported to be responsible for the preferential attraction and induction of regulatory T cells, creating an immune-regulatory microenvironment. 24,25 Next to the modulating effects of PGE2 on the effector mech...

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Prostaglandin E2 receptor activity and susceptibility to natural killer cells

Cited by 9 publications

References 18 publications

Lipid profile in actinic keratosis and basal cell carcinoma

Lipid profile in actinic keratosis and basal cell carcinoma

Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity

Inflammation restraining effects of prostaglandin E2 on natural killer–dendritic cell (NK-DC) interaction are imprinted during DC maturation

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