{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:01:49Z","timestamp":1790010109949,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T00:00:00Z","timestamp":1593734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005039","name":"Leids Universitair Medisch Centrum","doi-asserted-by":"publisher","award":["Ziena Abdulrahman received an MD\/PhD\u2010track grant."],"award-info":[{"award-number":["Ziena Abdulrahman received an MD\/PhD\u2010track grant."]}],"id":[{"id":"10.13039\/501100005039","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunotherapy of vulvar high\u2010grade squamous intraepithelial lesion (vHSIL) is investigated as an alternative for surgery, because of high comorbidity and risk of recurrence. Limited evidence exists on the role and composition of the immune microenvironment in current immunotherapeutic approaches for vHSIL. The vHSIL of 29 patients biopsied before treatment with imiquimod were analyzed by two multiplex seven\u2010color immunofluorescence panels to investigate the pre\u2010existing T\u2010cell and myeloid cell composition in relation to treatment response. The samples were scanned with the Vectra multispectral imaging system. Cells were automatically phenotyped and counted with inForm advanced image analysis software. Cell counts and composition were compared to that of vHSIL patients before therapeutic vaccination (n = 29) and to healthy vulva (n = 27). Our data show that the immune microenvironment of complete responders (CR) to imiquimod resembled the coordinated infiltration with type 1 CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells and CD14<jats:sup>+<\/jats:sup> inflammatory myeloid cells also found in healthy vulva. However, more CD8<jats:sup>+<\/jats:sup> T cells and FoxP3<jats:sup>+<\/jats:sup> regulatory T cells were present in CR. The lesions of partial responders (PR) lacked such a coordinated response and displayed an impaired influx of CD14<jats:sup>+<\/jats:sup> inflammatory myeloid cells. Importantly, complete responses after imiquimod or therapeutic vaccination showed the same dependency on a pre\u2010existing coordinated type 1 T\u2010cell and CD14<jats:sup>+<\/jats:sup> myeloid cell infiltration. In conclusion, a good clinical outcome after two different forms of immunotherapy for vHSIL is associated with the presence of a primary inflammatory process resulting in the coordinated influx of several types of immune cells which is then amplified.<\/jats:p>","DOI":"10.1002\/ijc.33168","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T20:29:05Z","timestamp":1592944145000},"page":"2914-2923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A pre\u2010existing coordinated inflammatory microenvironment is associated with complete response of vulvar high\u2010grade squamous intraepithelial lesions to different forms of immunotherapy"],"prefix":"10.1002","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9079-0293","authenticated-orcid":false,"given":"Ziena","family":"Abdulrahman","sequence":"first","affiliation":[{"name":"Department of Gynaecology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Pathology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Medical Oncology, Oncode Institute Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel F. C. C.","family":"de Miranda","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart W. J.","family":"Hellebrekers","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Haga Hospital  Den Haag The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy J.","family":"de Vos van Steenwijk","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith M. 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