{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:33:03Z","timestamp":1791048783445,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities such as surgery and radiotherapy. Methods: Peer-reviewed articles published between January 2000 and August 2025 were searched manually in four databases: Scopus, ScienceDirect, PubMed and MEDLINE, using the keywords \u201cMerkel cell carcinoma\u201d AND \u201cimmunotherapy\u201d AND \u201cimmune checkpoint inhibitors\u201d. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was employed. Results: ICIs can be given in different settings: (A) Neoadjuvant: The CheckMate 358 trial reported a 54.5% response rate among 33 radiologically evaluable patients treated with nivolumab, each showing over 30% tumor reduction. (B) Adjuvant: (1) The ADMEC-O phase II trial demonstrated improved disease-free survival with adjuvant nivolumab. (2) The ADAM phase III trial evaluates adjuvant avelumab in node-positive patients post-surgery\/radiation, with common side effects including nausea, fatigue, and itching. (3) STAMP, a phase III trial, investigates pembrolizumab in stage I\u2013III MCC. Both ADAM and STAMP have completed accrual and results are pending. (C) Primary therapy: KEYNOTE-017 and JAVELIN trials reported a 60% overall response rate and ~40% 3-year progression-free survival with first-line pembrolizumab or avelumab. Both agents also show promise as salvage therapies. Conclusions: ICIs demonstrate encouraging outcomes in MCC across various treatment stages. Continued research is essential to optimize treatment timing and integrate multimodal therapies.<\/jats:p>","DOI":"10.3390\/cancers17193272","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:31Z","timestamp":1760028871000},"page":"3272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immune Checkpoint Inhibitors in Merkel Cell Carcinoma of the Skin: A 2025 Comprehensive Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-776X","authenticated-orcid":false,"given":"Patricia","family":"Tai","sequence":"first","affiliation":[{"name":"Oncology Department, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9760-651X","authenticated-orcid":false,"given":"Omar","family":"Alqaisi","sequence":"additional","affiliation":[{"name":"Nursing Department, Al-Zaytoonah University, Amman P.O. Box 130, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8345-0140","authenticated-orcid":false,"given":"Suhair","family":"Al-Ghabeesh","sequence":"additional","affiliation":[{"name":"Nursing Department, Al-Zaytoonah University, Amman P.O. Box 130, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9309-9959","authenticated-orcid":false,"given":"Lorent","family":"Sijarina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Prishtina, 10000 Prishtina, Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-115X","authenticated-orcid":false,"given":"Edward","family":"Yu","sequence":"additional","affiliation":[{"name":"Oncology Department, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife Jones","family":"Thachuthara","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Cork University, T12 K8AF Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Assouline","sequence":"additional","affiliation":[{"name":"Oncology Department, Coll\u00e8ge de M\u00e9decine des H\u00f4pitaux de Paris, Cedex 12, 75 610 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Souied","sequence":"additional","affiliation":[{"name":"Oncology Department, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Hagel","sequence":"additional","affiliation":[{"name":"Oncology Department, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3514-2183","authenticated-orcid":false,"given":"Kurian","family":"Joseph","sequence":"additional","affiliation":[{"name":"Oncology Department, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41571-018-0103-2","article-title":"The biology and treatment of Merkel cell carcinoma: Current understanding and research priorities","volume":"15","author":"Harms","year":"2018","journal-title":"Nat. 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