Submit a comment
Abstract
BACKGROUND. 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. METHODS. 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–induced T cell immunity in the skin. RESULTS. Calcipotriol plus 5-FU–induced tissue-resident memory T (Trm) cell formation in face and scalp skin associated with significantly higher erythema scores compared with control (P < 0.01). Importantly, more participants in the test cohort remained SCC-free over the more than 1,500-day follow-up period (P = 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: 0.048–0.972], P = 0.032). Accordingly, significantly more epidermal Trm cells persisted in the calcipotriol plus 5-FU–treated face and scalp skin compared with control (P = 0.0028). There was no significant difference in BCC incidence between the treatment groups. CONCLUSION. 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. FUNDING. This research was supported by internal academic funds and by grants from the Burroughs Wellcome Fund, Sidney Kimmel Foundation, Cancer Research Institute, and NIH.
Authors
Abby R. Rosenberg, Mary Tabacchi, Kenneth H. Ngo, Michael Wallendorf, Ilana S. Rosman, Lynn A. Cornelius, Shadmehr Demehri
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
