Organ transplant recipients (OTRs) are disproportionately afflicted with premalignant and malignant skin lesions, with significant associated morbidity and mortality. Because of the intense immunosuppressive therapy necessary to sustain their grafts, the cutaneous malignancies they develop are more numerous and more dangerous than those of immunocompetent individuals. It is imperative that premalignant and localized malignant lesions are treated early in organ transplant recipients. Many modalities are utilized for this purpose, including surgical and nonsurgical approaches. The use of the topical immunomodulator imiquimod in OTRs is intriguing because it relies on the induction of a local immune response in patients with iatrogenically modified immune systems. However, it is important to consider whether this local immune induction poses a threat to the transplanted organ.

Imiquimod is a topical chemotherapeutic agent of the imidazoquinoline family. It is an immune response modifier with antitumor and antiviral properties that induces migration and activation of dendritic (antigen-presenting) cells. Imiquimod binds to and stimulates cell surface receptors, such as Toll-like receptors 7 and 9, on macrophages and other dendritic cells. These cells then secrete proinflammatory cytokines that tip the balance of the immune response to a cell mediated, or TH-1, mode. The cytokines secreted by the activated dendritic cells include interferon α (IFN-α), tumor necrosis factor α (TNF-α), and interleukins (IL) 1 and 12. These cytokines stimulate activated T cells to secrete IL-2 and IFN-γ which, in turn, induce more macrophage secretion of IL-12. A positive feedback mechanism is thus generated and is self-perpetuating.