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Transdermal microneedle (MN)\u2010based drug delivery systems have emerged as an interesting alternative for localized, minimally invasive melanoma immunotherapy in recent years. This review is a critical analysis of the recent breakthroughs in MN\u2010mediated immunotherapeutic models of melanoma, with a focus on the capability to: (1) regulate the tumor microenvironment (TME), (2) improve antitumor immunity, and (3) minimize the systemic adverse effects. The ability of various MN platforms, such as peptide supramolecular MNs, melanin\u2010assisted immunotherapeutic patches, and self\u2010locking MNs produced via micro\u2010stereolithography, to provide sustained, spatially regulated delivery of immune checkpoint inhibitors, adjuvants, and tumor\u2010associated antigens directly into the TME is discussed. A mechanistic understanding of immune activation cascades involving antigen\u2010presenting cell interactions, T\u2010cell priming, and immune memory establishment is illuminated. The review also examines strategies of synergistic combinations of MN\u2010based immunotherapy with photothermal therapy and chemotherapeutic co\u2010delivery to circumvent immune resistance and reprogram the immunosuppressive TME. Other important design factors, such as polymer composition, nanocarrier integration, and stimuli\u2010responsive release mechanisms, are also discussed. There is comparative preclinical evidence that MN\u2010based systems are superior to conventional intratumoral injections in terms of drug retention, immune cell infiltration, and tumor regression. Taken together, this review testifies to the high translational potential of microneedle technologies as highly accurate, patient\u2010acceptable, and multifunctional vehicles of next\u2010generation melanoma immunotherapy.<\/jats:p>","DOI":"10.1002\/ardp.70265","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:02:12Z","timestamp":1780383732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microneedle\u2010Assisted Skin Delivery of Immunotherapies for Melanoma"],"prefix":"10.1002","volume":"359","author":[{"given":"Issac V.","family":"Cherian","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Mustahidul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Akash","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Vijukumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Janvi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourabh","family":"Kosey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6295-1798","authenticated-orcid":false,"given":"Navjot Kaur","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Quality Assurance ISF College of Pharmacy Moga Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00565-7"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01854-3"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00687-1"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781003463191-12"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048747"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01325-0"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-022-02250-8"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c01895"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12045-022-1294-5"},{"key":"e_1_2_16_11_1","first-page":"327","article-title":"Emerging Applications of Polymers in Biomedical and Pharmaceutical Fields","author":"Chellathurai M. 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