{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:00:02Z","timestamp":1774684802262,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Vulvovaginal melanoma (VVM) is a rare malignancy with poor prognosis and limited evidence to guide immunotherapy selection. This study aimed to assess the expression and interrelationships of programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T-lymphocyte\u2013associated protein 4 (CTLA-4), cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8), and their associations with clinicopathological features and outcomes. Fifteen VVM cases were analysed using immunohistochemistry. PD-L1 was evaluated using tumour proportion score (TPS), immune cell score (IS), and combined positive score (CPS), CTLA-4, CD4, and CD8 were scored. Continuous marker values were analysed using Pearson correlation, with additional descriptive and spatial assessment of marker distribution\n                    <jats:bold>.<\/jats:bold>\n                    Survival and treatment data were reviewed when available. Most tumours showed high expression of PD-1, PD-L1 (IS\/CPS), CTLA-4, CD4, and CD8, whereas PD-L1 (TPS) was comparatively lower. Significant positive correlations were observed between PD-1 and CD8, PD-1 and PD-L1 (IS\/CPS), CD8 and PD-L1 (CPS), and between CTLA-4 and PD-L1 (TPS\/CPS), indicating coordinated immune-checkpoint activation. PD-L1 expression was frequently enriched at the tumour\u2013stroma interface. High CD4 expression correlated with increased mitotic rate, while CD8 and CTLA-4 expression correlated with melanin status. Higher PD-1, PD-L1, and CTLA-4 expression generally associated with longer overall survival following immunotherapy. In a case with serial recurrences, PD-1, PD-L1 (TPS, CPS), CTLA-4 expression increased while PD-L1 (IS) and CD4\u2009+\u2009\/CD8\u2009+\u2009ratio decreased, suggesting a progressively immunosuppressive tumour microenvironment. These findings suggest that integrated immune profiling of PD-1, PD-L1, CTLA-4, and T-cell subsets may serve as predictive markers for immunotherapy in VVM.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04494-2","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T07:35:45Z","timestamp":1774683345000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the immune landscape of melanoma of the lower female genital tract"],"prefix":"10.1007","author":[{"given":"Yuetong","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamia Sabry","family":"Aboelnasr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Lockett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srdjan","family":"Saso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-9618","authenticated-orcid":false,"given":"Mona","family":"El-Bahrawy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"4494_CR1","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1242\/dev.106567","volume":"142","author":"RL Mort","year":"2015","unstructured":"Mort RL, Jackson IJ, Patton EE (2015) The melanocyte lineage in development and disease. 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