{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:26:52Z","timestamp":1789810012351,"version":"4.0.1"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Health Holland","award":["LSHM18056-SGF"],"award-info":[{"award-number":["LSHM18056-SGF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tumor-derived prostaglandin E2 (PGE2) impairs antitumor immunity by priming suppressive functions on various immune cell types, including dendritic cells (DCs). In this way, tumors mediate DC dysfunction and hamper their antitumoral activity. PGE2 is known to modulate DC function via signaling through the E-type prostanoid receptor 2 (EP2) and EP4. Preclinical studies have demonstrated the therapeutic value of targeting EP2\/4 receptor signaling in DCs. Ongoing phase 1 clinical trials with EP antagonists have shown immunomodulation in cancer patients. However, the systemic drug administration leads to off-target events and subsequent side effects. To limit the off-target effects of EP targeting, EP2 and EP4 antagonists were encapsulated in polymeric nanoparticles (NPs). In this study, we evaluated the efficacy of EP2\/4-specific antagonists encapsulated in NPs to protect conventional type 2 DCs (cDC2s) from suppressive effects of tumor-derived PGE2 in different tumor models. We show that tumor-derived PGE2 signals via EP2\/4 to mediate the acquisition of a suppressive phenotype of cDC2s. EP2\/4 antagonists encapsulated in NPs impaired the conversion of cDC2s toward a suppressive state and inhibited the occurrence of suppressive features such as interleukin-10 production or the ability to expand regulatory T cells. Importantly, the NPs abolished the transition toward this suppressive state in different tumor models: melanoma-conditioned media, ascites fluid derived from ovarian cancer patients (2-dimensional), and upon coculture with colorectal cancer patient\u2013derived organoids (3-dimensional). We propose that targeting the PGE2-EP2\/4 axis using NPs can achieve immunomodulation in the immune system of cancer patients, alleviate tumor-derived suppression, and thus facilitate the development of potent antitumor immunity in cancer patients.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae164","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T12:19:55Z","timestamp":1721737195000},"page":"1554-1567","source":"Crossref","is-referenced-by-count":17,"title":["EP2\/EP4 targeting prevents tumor-derived PGE2-mediated immunosuppression in cDC2s"],"prefix":"10.1093","volume":"116","author":[{"given":"Jorge","family":"Cuenca-Escalona","sequence":"first","affiliation":[{"name":"Department of Medical BioSciences, Radboud University Medical Center , Geert Grooteplein 28, 6525 GA, Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"B\u00f6dder","sequence":"additional","affiliation":[{"name":"Department of Medical BioSciences, Radboud University Medical Center , Geert Grooteplein 28, 6525 GA, Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Subtil","sequence":"additional","affiliation":[{"name":"Department of Medical BioSciences, Radboud University Medical Center , Geert Grooteplein 28, 6525 GA, Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"S\u00e1nchez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Medical BioSciences, Radboud University Medical Center , Geert Grooteplein 28, 6525 GA, Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Vidal-Manrique","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology, Radboud University Medical Center , Geert Grooteplein Zuid 10, 6525 GA, Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W D","family":"Sweep","sequence":"additional","affiliation":[{"name":"Department of Medical BioSciences, Radboud University Medical Center , Geert Grooteplein 28, 6525 GA, Nijmegen ,","place":["the Netherlands"]},{"name":"Department of Medical Oncology, Radboud University Medical Center , Geert Grooteplein Zuid 10, 6525 GA, Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Fauerbach","sequence":"additional","affiliation":[{"name":"R&D Reagents, Chemical Biology Department; Miltenyi Biotec B.V. & Co. 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