{"id":4426,"date":"2025-12-17T10:01:44","date_gmt":"2025-12-17T03:01:44","guid":{"rendered":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/?p=4426"},"modified":"2026-03-30T15:44:08","modified_gmt":"2026-03-30T08:44:08","slug":"prostaglandin-e2-ep2-ep4-signaling-induces-immunosuppression-in-human-cancer-by-impairing-bioenergetics-and-ribosome-biogenesis-in-immune-cells","status":"publish","type":"post","link":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/prostaglandin-e2-ep2-ep4-signaling-induces-immunosuppression-in-human-cancer-by-impairing-bioenergetics-and-ribosome-biogenesis-in-immune-cells\/","title":{"rendered":"Prostaglandin E2-EP2\/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells"},"content":{"rendered":"<p>Siwakorn Punyawatthananukool, Ryuma Matsuura, Thamrong Wongchang , Nao Katsurada, Tatsuaki Tsuruyama, Masaki Tajima, Yutaka Enomoto, Toshio Kitamura, Masahiro Kawashima, Masakazu Toi, Koji Yamanoi, Junzo Hamanishi, Shigeo Hisamori, Kazutaka Obama, <strong>Varodom Charoensawan<\/strong>, Dean Thumkeo, Shuh Narumiya<\/p>\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<div class=\"title\">\n<p>While prostaglandin E2 (PGE2) is produced in human tumor microenvironment (TME), its role therein remains poorly understood. Here, we examine this issue by comparative single-cell RNA sequencing of immune cells infiltrating human cancers and syngeneic tumors in female mice. PGE receptors EP4 and EP2 are expressed in lymphocytes and myeloid cells, and their expression is associated with the downregulation of oxidative phosphorylation (OXPHOS) and MYC targets, glycolysis and ribosomal proteins (RPs). Mechanistically, CD8+ T cells express EP4 and EP2 upon TCR activation, and PGE2 blocks IL-2-STAT5 signaling by downregulating Il2ra, which downregulates c-Myc and PGC-1 to decrease OXPHOS, glycolysis, and RPs, impairing migration, expansion, survival, and antitumor activity. Similarly, EP4 and EP2 are induced upon macrophage activation, and PGE2 downregulates c-Myc and OXPHOS in M1-like macrophages. These results suggest that PGE2-EP4\/EP2 signaling impairs both adaptive and innate immunity in TME by hampering bioenergetics and ribosome biogenesis of tumor-infiltrating immune cells.<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39487111\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/39487111\/<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Siwakorn Punyawatthananukool, Ryuma Matsuura, Thamrong Wongchang , Nao Katsurada, Tatsuaki Tsuruyama, Masaki Tajima, Yutaka Enomoto, Toshio Kitamura, Masahiro Kawashima, Masakazu Toi, Koji Yamanoi, Junzo Hamanishi, Shigeo Hisamori, Kazutaka Obama, Varodom Charoensawan, Dean Thumkeo, Shuh Narumiya Abstract While prostaglandin E2 (PGE2) is produced in human tumor microenvironment (TME), its role therein remains poorly understood. Here, we [&#8230;]\n","protected":false},"author":6,"featured_media":4428,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-4426","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-innovation-en"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Prostaglandin E2-EP2\/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/prostaglandin-e2-ep2-ep4-signaling-induces-immunosuppression-in-human-cancer-by-impairing-bioenergetics-and-ribosome-biogenesis-in-immune-cells\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Prostaglandin E2-EP2\/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"og:description\" content=\"Siwakorn Punyawatthananukool, Ryuma Matsuura, Thamrong Wongchang , Nao Katsurada, Tatsuaki Tsuruyama, Masaki Tajima, Yutaka Enomoto, Toshio Kitamura, Masahiro Kawashima, Masakazu Toi, Koji Yamanoi, Junzo Hamanishi, Shigeo Hisamori, Kazutaka Obama, Varodom Charoensawan, Dean Thumkeo, Shuh Narumiya Abstract While prostaglandin E2 (PGE2) is produced in human tumor microenvironment (TME), its role therein remains poorly understood. Here, we [...]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/prostaglandin-e2-ep2-ep4-signaling-induces-immunosuppression-in-human-cancer-by-impairing-bioenergetics-and-ribosome-biogenesis-in-immune-cells\/\" \/>\n<meta property=\"og:site_name\" content=\"\u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/SIBBprogram\/\" \/>\n<meta property=\"article:published_time\" content=\"2025-12-17T03:01:44+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-03-30T08:44:08+00:00\" \/>\n<meta property=\"og:image\" 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