Skin cancer precursor immunotherapy for squamous cell carcinoma prevention

JCI Insight. 2019 Mar 21;4(6):e125476. doi: 10.1172/jci.insight.125476.

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.

Keywords: Adaptive immunity; Cancer immunotherapy; Dermatology; Oncology; Skin cancer.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Calcitriol / analogs & derivatives
  • Calcitriol / pharmacology
  • Calcitriol / therapeutic use
  • Carcinoma, Basal Cell
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Double-Blind Method
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Immunotherapy / methods*
  • Male
  • Middle Aged
  • Prospective Studies
  • Skin / immunology
  • Skin / pathology
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*

Substances

  • calcipotriene
  • Calcitriol
  • Fluorouracil