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RRP is characterized by multiple abnormalities in innate and adaptive immunity. Natural killer (NK) cells play important roles in immune surveillance and are\u00a0part of the innate immune responses that help prevent tumor growth. We identified that papillomas lack classical class I MHC and retain nonclassical class I MHC expression. Moreover, in this study, we have identified and characterized the mechanism that blocks NK cell targeting of papilloma cells. Here, we show for the first time that the PGE\n                    <jats:sub>2<\/jats:sub>\n                    secreted by papilloma cells directly inhibits NK cells activation\/degranulation principally through the PGE\n                    <jats:sub>2<\/jats:sub>\n                    receptor EP2, and to a lesser extent through EP4 signaling. Thus, papilloma cells have a potent mechanism to block NK cell function that likely supports papilloma cell growth.\n                  <\/jats:p>","DOI":"10.1002\/eji.202250036","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T14:38:00Z","timestamp":1673015880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PGE\n                    <sub>2<\/sub>\n                    expression by HPV6\/11\u2010induced respiratory papillomas blocks NK cell activation in patients with recurrent respiratory papillomatosis"],"prefix":"10.1002","volume":"53","author":[{"given":"Mohd","family":"Israr","sequence":"first","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fung","family":"Lam","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"DeVoti","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily M.","family":"Mace","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Vagelos College of Physicians and Surgeons Columbia Medical Center  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Papayannakos","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Abramson","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettie M.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent R.","family":"Bonagura","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research Northwell Health  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.17.5425"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.2.560"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e328316930e"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2007.12.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e31816a7135"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2010.02617.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2004.05.014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2009.10.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4784"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.12.789"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2276"},{"key":"e_1_2_9_13_1","first-page":"73","article-title":"Natural killer cells: role in local tumor growth and metastasis","volume":"6","author":"Langers I.","year":"2012","journal-title":"Biologics"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061553"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00176"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103478"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1992.01880010029011"},{"key":"e_1_2_9_18_1","volume-title":"Papillomavirus: molecular and clinical aspects, Alan R. 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