{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T05:29:14Z","timestamp":1782624554104,"version":"3.54.5"},"reference-count":27,"publisher":"American Society for Clinical Investigation","issue":"6","funder":[{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","award":["Career Award for Medical Scientists"],"award-info":[{"award-number":["Career Award for Medical Scientists"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["K08AR068619"],"award-info":[{"award-number":["K08AR068619"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["DP5OD0213530"],"award-info":[{"award-number":["DP5OD0213530"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006156","name":"Sidney Kimmel Foundation for Cancer Research","doi-asserted-by":"crossref","award":["Scholar award"],"award-info":[{"award-number":["Scholar award"]}],"id":[{"id":"10.13039\/100006156","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cancer Research Institute","award":["CLIP"],"award-info":[{"award-number":["CLIP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,21]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    We performed a blinded prospective cohort study on participants of a randomized double-blind clinical trial in which a 4-day course of topical calcipotriol plus 5-FU combination was compared to Vaseline plus 5-FU (control) for AK treatment. SCC and basal cell carcinoma (BCC) incidences were assessed at 1, 2, and 3 years after trial. Tissues were analyzed for calcipotriol plus 5-FU\u2013induced T cell immunity in the skin.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Calcipotriol plus 5-FU\u2013induced tissue-resident memory T (Trm) cell formation in face and scalp skin associated with significantly higher erythema scores compared with control (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01). Importantly, more participants in the test cohort remained SCC-free over the more than 1,500-day follow-up period (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0765), and significantly fewer developed SCC on the treated face and scalp within 3 years (2 of 30 [7%] versus 11 of 40 [28%] in control group, hazard ratio 0.215 [95% CI: 0.048\u20130.972],\n                    <jats:italic>P<\/jats:italic>\n                    = 0.032). Accordingly, significantly more epidermal Trm cells persisted in the calcipotriol plus 5-FU\u2013treated face and scalp skin compared with control (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0028). There was no significant difference in BCC incidence between the treatment groups.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    A short course of calcipotriol plus 5-FU treatment on the face and scalp is associated with induction of robust T cell immunity and Trm formation against AKs and significantly lowers the risk of SCC development within 3 years of treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    This research was supported by internal academic funds and by grants from the Burroughs Wellcome Fund, Sidney Kimmel Foundation, Cancer Research Institute, and NIH.\n                  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