Immunotherapy for Pre-Cancerous Lesions May Reduce Skin Cancer Risk Over Time


The combination therapy reduced the risk of squamous cell carcinoma development on the face and scalp by approximately 75% in the study.

An immunotherapy combination consisting of 2 FDA-approved drugs that have previously been shown to clear precancerous skin lesions known as actinic keratosis (AK) may also reduce the risk of developing squamous cell carcinomas (SCCs) over time, according to a new study.

The study, published in JCI Insight, demonstrated that topical calcipotriol plus 5-fluorouracil (5-FU) combination therapy reduced the risk of SCC development on the face and scalp by approximately 75%. The treatment is an effective immunotherapy against AK, which is a precursor to SCC.

Cutaneous SCC is the second most common type of cancer. AKs, which commonly develop in sun-damaged skin, can result in a higher risk of developing SCC if left untreated. Typically, these lesions are treated with therapies directed against the individual lesions, such as cryotherapy, and field treatments, including photodynamic therapy and topical 5-FU, imiquimod, diclofenac, and ingenol mebutate, according to the study. However, the ability of these treatments to prevent SCC in the long term after treatment has ceased is unclear.

The calcipotriol plus 5-FU combination, which is approved for the treatment of psoriasis, has previously been identified as a novel topical immunotherapy for AK. Although a previous study implicated its effect on treating these skin cancer precursors, it remained unknown whether this effect translated into a decreased risk of SCC over time, according to the study researchers.

In the current study, which follows up on patients from the previous trial conducted in 2017, the researchers compared a 4-day course of topical calcipotriol plus 5-FU combination with Vaseline plus 5-U for AK treatment. They assessed SCC and basal cell carcinoma (BCC) incidences at 1, 2, and 3 years after the trial. Of the 130 patients in the original trial, 3-year outcome results were available for 84 and results for treatment on the face and scalp were available for 72 patients.

Overall, the study showed that calcipotriol plus 5-FU-induced tissue-resident memory T (Trm) cell formation in face and scalp skin was associated with significantly higher erythema scores compared with the control group. Additionally, more patients who were treated with the combination remained SCC-free over the follow-up period, which lasted more than 1500 days, and significantly fewer developed SCC on the treated face and scalp within 3 years.

The study also showed significantly more epidermal Trm cells persisted in the calcipotriol plus 5-FU-treated face and scalp skin compared with patients in the control arm. Only 7% of patients in the calcipotriol plus 5-FU group developed SCC compared with 28% in the control group, according to the data.

The researchers did not find any significant difference in BCC incidence between the 2 treatment groups.

However, the treatment did not reduce SCC development on the arms. The researchers noted that this may be due to greater immune system activation on the face and scalp, as well as better penetration of topical treatments on those areas.

“The primary reason for treating actinic keratosis is to prevent SCC development, and our findings suggest this immunotherapy may be an effective way of achieving that goal,” senior author Shawn Demehri, MD, PhD, of the MGH Center for Cancer Immunology and the Cutaneous Biology Research Center, said in a press release. “Finding that targeting precancerous lesions with a robust T-cell-directed immunotherapy can yield effective cancer prevention may be applicable to other organs than the skin, something we hope to investigate for malignancies such as breast cancer, for which immunoprevention is an urgent, unmet need.”


Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insights. 2019. Doi: 10.1172/jci.insight.125476

Immunotherapy of precancerous skin lesions may prevent squamous cell carcinoma [news release]. Massachusetts General Hospital. Accessed March 21, 2019.

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