Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation
Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We fo...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01859/full |
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doaj-3b032f0ea64c4ba78f35f52b49294f7d2020-11-25T00:10:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01859363999Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell DifferentiationArum Park0Arum Park1Yunhee Lee2Yunhee Lee3Mi Sun Kim4Young Ju Kang5Young-Jun Park6Young-Jun Park7Haiyoung Jung8Haiyoung Jung9Tae-Don Kim10Tae-Don Kim11Hee Gu Lee12Hee Gu Lee13Inpyo Choi14Inpyo Choi15Suk Ran Yoon16Suk Ran Yoon17Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Biochemistry, College of Pharmacy, Chungnam National University, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaNew Drug Development Center, OSONG Medical Innovation Foundation, Cheongju-si, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Functional Genomics, University of Science & Technology, Daejeon, South KoreaNatural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We found that prostaglandin (PG) E2 produced by thyroid cancer cells suppressed the cytolytic activity of NK cells by inhibiting the expression of the natural cytotoxicity receptors NKp44 and NKp30 and the death receptor tumor necrosis factor-related apoptosis-inducing ligand. PGE2 and cyclooxygenase-2 were highly expressed in thyroid cancer cells; moreover, anaplastic thyroid cancer cells released higher amounts of PGE2 than the papillary subtype, which was associated with suppression of NK cell-inducing nuclear factor-κB and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways via PGE2 receptor (EP) 2 and EP4 expressed on the NK cell surface. In addition, PGE2 inhibited the functional maturation of NK cells and reduced their cytotoxicity against target cells. These results indicate that PGE2 promotes thyroid cancer progression by inhibiting NK cell maturation and cytotoxicity. Thus, therapeutic strategies that target PGE2 in thyroid cancer could potentiate the immune response and improve patient prognosis.https://www.frontiersin.org/article/10.3389/fimmu.2018.01859/fullprostaglandin E2thyroid cancernatural killer cellimmune escapecytotoxicitydifferentiation |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Arum Park Arum Park Yunhee Lee Yunhee Lee Mi Sun Kim Young Ju Kang Young-Jun Park Young-Jun Park Haiyoung Jung Haiyoung Jung Tae-Don Kim Tae-Don Kim Hee Gu Lee Hee Gu Lee Inpyo Choi Inpyo Choi Suk Ran Yoon Suk Ran Yoon |
| spellingShingle |
Arum Park Arum Park Yunhee Lee Yunhee Lee Mi Sun Kim Young Ju Kang Young-Jun Park Young-Jun Park Haiyoung Jung Haiyoung Jung Tae-Don Kim Tae-Don Kim Hee Gu Lee Hee Gu Lee Inpyo Choi Inpyo Choi Suk Ran Yoon Suk Ran Yoon Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation Frontiers in Immunology prostaglandin E2 thyroid cancer natural killer cell immune escape cytotoxicity differentiation |
| author_facet |
Arum Park Arum Park Yunhee Lee Yunhee Lee Mi Sun Kim Young Ju Kang Young-Jun Park Young-Jun Park Haiyoung Jung Haiyoung Jung Tae-Don Kim Tae-Don Kim Hee Gu Lee Hee Gu Lee Inpyo Choi Inpyo Choi Suk Ran Yoon Suk Ran Yoon |
| author_sort |
Arum Park |
| title |
Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation |
| title_short |
Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation |
| title_full |
Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation |
| title_fullStr |
Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation |
| title_full_unstemmed |
Prostaglandin E2 Secreted by Thyroid Cancer Cells Contributes to Immune Escape Through the Suppression of Natural Killer (NK) Cell Cytotoxicity and NK Cell Differentiation |
| title_sort |
prostaglandin e2 secreted by thyroid cancer cells contributes to immune escape through the suppression of natural killer (nk) cell cytotoxicity and nk cell differentiation |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2018-08-01 |
| description |
Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We found that prostaglandin (PG) E2 produced by thyroid cancer cells suppressed the cytolytic activity of NK cells by inhibiting the expression of the natural cytotoxicity receptors NKp44 and NKp30 and the death receptor tumor necrosis factor-related apoptosis-inducing ligand. PGE2 and cyclooxygenase-2 were highly expressed in thyroid cancer cells; moreover, anaplastic thyroid cancer cells released higher amounts of PGE2 than the papillary subtype, which was associated with suppression of NK cell-inducing nuclear factor-κB and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways via PGE2 receptor (EP) 2 and EP4 expressed on the NK cell surface. In addition, PGE2 inhibited the functional maturation of NK cells and reduced their cytotoxicity against target cells. These results indicate that PGE2 promotes thyroid cancer progression by inhibiting NK cell maturation and cytotoxicity. Thus, therapeutic strategies that target PGE2 in thyroid cancer could potentiate the immune response and improve patient prognosis. |
| topic |
prostaglandin E2 thyroid cancer natural killer cell immune escape cytotoxicity differentiation |
| url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01859/full |
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