Skin cancer precursor immunotherapy for squamous cell carcinoma prevention

Abstract

Conflict of interest: LAC and SD are co-inventors on a filed patent for the use of calcipotriol plus 5-fluorouracil for the treatment of precancerous skin lesions (PCT/US2015/049434).

Protective and pathogenic roles of resident memory T cells in human skin disorders

“…The maintenance of T RM reacting with melanoma antigens in the vitiligo lesions, which indicates good prognosis, of melanoma patients [44] at least suggests the protective function of this T RM population against disease development. It has also been reported that T RM induction in actinic keratosis prevents the development of squamous cell carcinoma, demonstrating the antitumor efficacy of TIL with the T RM phenotype [50]. Further functional analyses are needed.…”

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention

“…A 2e4 weeks course appeared to have a protective effect for one year, with non-significant effect thereafter. Addition of calcipotriol to 5-FU has been shown to increase the benefit [179]. Topical tretinoin has no significant effect in preventing cSCC [180].…”

Treatment of porokeratosis of Mibelli with combined use of topical fluorouracil and calcipotriene

“…The 5-FU/calcipotriene combination has previously been shown in mouse models to stimulate expression of thymic stromal lymphopoietin and synergistically activate CD4 + T cell-mediated immunity against actinic keratoses, thereby reducing the incidence of squamous cell carcinoma in treated areas. 4 , 5 Topical 5- FU/calcipotriene has also been reported as an effective treatment option for refractory extramammary Paget disease, presumably through a similar synergistic activation of T cell anti-tumor immunity. 6 …”

“…Importantly, by generating T cell-mediated immunity against actinic keratoses, topical 5-FU/calcipotriene is thought to potentially establish an anti-tumor immune memory via skin-resident T cells, thereby affording long-term skin cancer suppression. 5 Indeed, Rosenberg et al found that 5-FU/calcipotriene prevented squamous cell carcinoma development on the face and scalp within 3 years after treatment. 5 While this case demonstrates the efficacy of topical 5-FU/calcipotriene in stimulating a localized immune response to successfully treat PM in an immunocompromised patient, it would be helpful to determine whether this combination similarly reduces skin cancer development in this high-risk population.…”

“…The combination of 5-FU/calcipotriene has been shown to have a synergistic effect in activating CD4 + T cell-mediated immunity against actinic keratoses and squamous cell carcinomas, resulting in a sustained effect. 4 , 5 We hypothesized that a similarly effective immune response may be seen in treating PM. Here we present a transplant patient who experienced complete clearance of his PM after application of topical 5-FU/calcipotriene.…”