Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod

Abstract

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.

The Role of Toll-like Receptor Agonists and Their Nanomedicines for Tumor Immunotherapy

“…A study performed by Oyama et al demonstrated that the number of mast cells elevated with R837 in the treatment of actinic keratosis injury. The present result suggests that mast cells may suppress human skin cancer treated with topical R837 [48], which can induce apoptosis, cell cycle changes, and the up-regulation of myeloid differentiation markers in some cell lines [49]. Although R837 binds well to TLR7, it binds less effectively to TLR8, which led to the development of the TLR7/8 agonist MEDI9197 (3M-052).…”

Rare Cutaneous Side Effects of Imiquimod: A Review on Its Mechanisms, Diagnosis, and Management

“…Furthermore, Tsutsumi et al [ 55 ] reported a case of imiquimod-induced psoriasis in which the eruptions resolved with a decrease in TNF-α levels after infliximab treatment, indicating that TNF-α also plays an important role in psoriasis associated with imiquimod. In addition, the levels of mast cells, which release various cytokines that trigger psoriasis, can be increased in lesions after the use of topical imiquimod [ 54 , 61 ]. Furthermore, the exacerbation of preexisting psoriasis may be partly attributed to the tissue-resident memory T cells [ 57 ].…”

The emerging role of mast cells in skin cancers: involved cellular and molecular mechanisms

“…67,68 Oyama et al after investigating MCD in AK lesions concluded that increased MCD in the lesions after treating with imiquimod (a TLR-7 agonist) is associated with the orchestration of an antitumor response. 69 The mechanism of action may be the involvement of toll-like receptor (TLR7 & 8) stimulation by imiquimod and production of TNFa by MCs. 69…”

“…69 The mechanism of action may be the involvement of toll-like receptor (TLR7 & 8) stimulation by imiquimod and production of TNFa by MCs. 69…”