Immunotherapy of basal cell carcinoma: evolving approaches

Nonmelanoma skin cancer (NMSC) is one of the most common types of cancer in the world. There is strong evidence that ultraviolet (UV) light plays a central role in the molecular pathogenesis of NMSC development. UV light causes DNA damage and loss of activity of tumor suppressor genes and overexpression of oncogenes and other genes related to enhanced growth and survival as well as tissue invasion. Also, UV light impairs the cutaneous immune response, especially Langerhans cell antigen-presenting function, resulting in immune tolerance to developing tumor cells. Standard treatments for NMSC include surgical excision, curettage and electrodessication, and Moh's micrographic surgery. Immunotherapy of NMSC has been attempted in the form of dinitrobenzene sensitization followed by topical application on the tumor, intralesional interferon injections, or perilesional interleukin-2. These treatments, although showing promise, have not been developed because of lower efficacy compared with surgical approaches, morbidity associated with treatments, as well as the expense of using recombinant cytokine treatments. The topical immune response modifier imiquimod is being developed as a novel local treatment for selected NMSC. Studies of the mechanism of action of imiquimod in NMSC indicate the presence of activated, natural killer cells (innate immunity), T-lymphocytes (adaptive immunity), antigen-presenting cells, and cytokines consistent with a delayed-type hypersensitivity reaction (Th1-lymphocyte cytokine pattern). This agent has been associated with a high response rate for the treatment of superficial basal cell carcinoma, with clearance rates ranging from 70% to 90% in a number of clinical trials. This novel immunotherapy represents a new, nonsurgical treatment option in the care of patients with NMSC.