Immunotherapy Directed Against Precancerous Skin Lesions May Prevent Squamous Cell Carcinoma
A treatment previously shown to treat the precancerous skin lesions called actinic keratosis now appears to also reduce the chance that these pretreated lesions will develop into squamous cell carcinoma. In a report published by Rosenberg et al in JCI Insight, researchers found that treatment with the combination of a topical chemotherapy and an immune system–activating compound reduced the risk of squamous cell carcinoma development on the face and scalp by almost 75%.
“This finding provides the first clinical proof-of-concept that an immunotherapy directed against premalignant tumors can prevent cancer,” said senior study author Shawn Demehri, MD, PhD, of the Massachusetts General Hospital Center for Cancer Immunology and the Cutaneous Biology Research Center. “We hope our findings will establish that the use of premalignant lesions as personalized therapeutic targets can train the immune system against the progression to cancer.”
Study Background
Actinic keratosis is a common lesion that develops in sun-damaged skin. While the chance of an individual lesion progressing to cancer is only 1%, the majority of squamous cell carcinomas develop from existing actinic keratosis lesions. In a study published in the January 2017 issue of the Journal of Clinical Investigation, Dr. Demehri and his team reported that twice-daily treatment for 4 days with a combination of calcipotriol—a U.S. Food and Drug Administration–approved treatment for psoriasis—and fluorouracil (5-FU) cream—a standard treatment for actinic keratosis—significantly reduced the number and size of actinic keratosis lesions.
The current study follows up on the participants of the 2017 trial to determine whether or not the combined treatment reduced the risk of their developing squamous cell carcinomas. Of the 130 participants in original trial, 3-year outcome results were available for 84 individuals—39 who received calcipotriol plus 5-FU and 45 who received a control treatment of 5-FU in petroleum jelly. Results for treatment on the face and scalp were available for 72 participants (32 who received the combination treatment and 40 controls).
Results
Overall, a greater proportion of participants who received the combination treatment for lesions on their face and scalp remained free of squamous cell carcinomas for more than 3 years after treatment. Seven percent of patients in the combination treatment group developed squamous cell carcinoma, compared with 28% in the control group. Samples of treated face and scalp tissues of 22 participants showed higher levels of tissue-resident memory T cells in normal skin treated with the combination treatment when compared with the control group.
While treatment did not reduce squamous cell carcinoma development on the arms, the investigators believe that may result from greater immune system activation on the face and scalp along with better penetration of topical treatments on those areas. They hypothesize that longer treatment with calcipotriol plus 5-FU may be required to reduce squamous cell carcinoma risk on the arms and other parts of the body.
“Our previous findings that calcipotriol plus 5-FU is highly effective for actinic keratosis clearance has led to its being increasingly used in clinics around the world, although further clinical studies are required for formal FDA approval,” said Dr. Demehri, an Assistant Professor of Dermatology at Harvard Medical School. “The treatment of squamous cell carcinoma can be costly and has significant side effects, and it can be deadly, particularly for patients with suppressed immune systems.”
“The primary reason for treating actinic keratosis is to prevent squamous cell carcinoma development, and our findings suggest this immunotherapy may be an effective way of achieving that goal,” he added. “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.”
Disclosure: The study authors' full disclosures can be found at insight.jci.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
