Topical imiquimod treatment of a cutaneous melanoma metastasis

Steinmann, Alexander; Funk, Jens Oliver; Schuler, Gerold; Driesch, Peter Von Den

doi:10.1067/mjd.2000.107954

Cited by 79 publications

(97 citation statements)

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“…We also investigated whether imiquimod, similarly to the human situation (51)(52)(53), can induce the regression of superficial melanocytic neoplasms of the skin and, if so, whether this phenomenon can be correlated with a particular phenotypic profile of leukocytes invading and surrounding the tumor. We observed that imiquimod treatment leads either to complete resolution or to a significant reduction of the tumors.…”

Section: Discussionmentioning

confidence: 99%

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Identification and Characterization of pDC-Like Cells in Normal Mouse Skin and Melanomas Treated with Imiquimod

Palamara

Meindl

Holcmann

et al. 2004

The Journal of Immunology

182

162

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Among the different subsets of dendritic cells (DC) described in humans and mice, epidermal Langerhans cells and dermal DCs represent the only DC populations resident in normal skin. In this study we describe a population of CD4+CD3− plasmacytoid DC (pDC)-like cells that accumulate in the dermis and spleens of mice topically treated with imiquimod, a low m.w. immune response modifier with potent antiviral and antitumor activities. These CD4+CD3− cells coexpress GR-1, B220, MHC class II, and, to a lesser extent, CD11c and display the phenotypic features of pDCs described in lymphoid organs. The accumulation of pDC-like cells after imiquimod treatment was detected not only in normal skin, but also in intradermally induced melanomas. Imiquimod treatment leads either to complete regression or to a significant reduction of the tumors. The number of pDCs correlates well with the clinical response of the tumors to the drug, suggesting that the antitumor effects of imiquimod could be mediated at least in part by the recruitment of pDC-like cells to the skin. Therefore, strategies aimed at activating and directing these cells into neoplastic tissues may be a promising and novel approach for the immunotherapy of various types of cancer.

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Section: Discussionmentioning

confidence: 99%

“…The immune response modifier imiquimod has been shown to exert antiviral and antitumor activities in both animal models and man (32,40,(51)(52)(53). Imiquimod is a potent cytokine inducer (33,37,38,54), and this activity is at least in part responsible for its clinical effects.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of pDC-Like Cells in Normal Mouse Skin and Melanomas Treated with Imiquimod

Palamara

Meindl

Holcmann

et al. 2004

The Journal of Immunology

182

162

View full text Add to dashboard Cite

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“…In addition, several controlled clinical trials as well as many smaller series of cases and case reports have demonstrated that imiquimod is also effective against a variety of primary skin cancers as well as cutaneous metastases of some malignancies. Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas (Sterry et al, 2002;BathHextall et al, 2004;Geisse et al, 2004;Gollnick et al, 2005;Schulze et al, 2005), keratoacanthomas (Dendorfer et al, 2003;Peris et al, 2003), actinic keratoses (Stockfleth et al, 2001(Stockfleth et al, , 2002Lebwohl et al, 2004;Szeimies et al, 2004;Korman et al, 2005) and Bowen's disease (the latter two entities represent epidermal carcinoma in situ) (Patel et al, 2006;Peris et al, 2006), cutaneous metastases of melanoma (Steinmann et al, 2000;Bong et al, 2002;Ugurel et al, 2002;Wolf et al, 2003;Zeitouni et al, 2005), some cases of primary melanoma in situ (Fleming et al, 2004;Kamin et al, 2005;Ray et al, 2005;Wolf et al, 2005;Lonsdale-Eccles et al, 2006) and cutaneous T-cell lymphomas (Suchin et al, 2002;Dummer et al, 2003b;Chong et al, 2004;Deeths et al, 2005). Clinical responses of cutaneous neoplasias to topical treatment with imiquimod have also been observed in difficult-to-treat patient populations, such as organ transplant patients under immunosuppressive therapy (Smith et al, 2001;Prinz et al, 2004;Brown et al, 2005) or Xeroderma pigmentosum patients suffering from rapid development of multiple UV-induced cutaneous malignancies …”

Section: Antitumoral Efficacy Of Tlr7/8 Agonists In Clinical Trialsmentioning

confidence: 99%

TLR7 and TLR8 as targets in cancer therapy

2008

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Small-molecule agonists at Toll-like receptor 7 (TLR7) and TLR8 have sparked a vivid interest in cancer research owing to their profound antitumoral activity. The lead compound of the imidazoquinoline family, imiquimod, is marketed as a topical formulation. It is efficacious against many primary skin tumors and cutaneous metastases. Using different imidazoquinoline species, distinct functions of TLR7 and TLR8 have been discovered. The predominant antitumoral mode of action of these agents is TLR7/ 8-mediated activation of the central transcription factor nuclear factor-jB, which leads to induction of proinflammatory cytokines and other mediators. Cutaneous dendritic cells are the primary responsive cell type and initiate a strong Th1-weighted antitumoral cellular immune response. Recent research has shown that dendritic cells themselves acquire direct antitumoral activity upon stimulation by imiquimod. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of TLR7/8. The proinflammatory activity of imiquimod, but not resiquimod, appears to be augmented by suppression of a regulatory mechanism, which normally limits inflammatory responses. This is achieved independently of TLR7/8 through interference with adenosine receptor signaling pathways. Finally, at higher concentrations imiquimod exerts Bcl-2-and caspase-dependent proapoptotic activity against tumor cells.

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“…14,15 Topical application of imiquimod, a recently introduced immune response modifier, has been shown to result in complete clinical and histopathologic regression in an 88-year-old woman with LM after 7 months of treatment and in a 50-year-old woman with disseminated cutaneous metastatic melanoma lesions. 8,16 In our 2 patients, tazarotene 0.1% gel demonstrated a high therapeutic efficacy and tolerability for treatment of LM. Complete regression, as assessed by clinical and histopathologic examinations, was observed after 6 and 8 months of treatment, respectively.…”

Section: Discussionmentioning

confidence: 99%

Treatment of lentigo maligna with tazarotene 0.1% gel

Chimenti

Carrozzo

Citarella

et al. 2004

Journal of the American Academy of Dermatology

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We report 2 elderly patients with facial lentigo maligna who experienced complete regression, both clinically and histopathologically, after once-daily topical treatment with tazarotene 0.1% gel for 6 to 8 months. After a follow-up period of 18 and 30 months, no recurrence was observed. We believe that tazarotene might be considered as an alternative medical approach in selected patients with lentigo maligna. (J Am Acad Dermatol 2004;50:101-3.) L entigo maligna (LM) is considered an in situ melanoma, clinically appearing as a patch with variegate color and irregular margins, located on sun-exposed areas of middle-aged or elderly patients. It is characterized by a slow radial growth phase, followed in some cases and after several months to years, by development of invasive melanoma. The risk for invasive LM increases in lesions larger than 1.5 cm in diameter. The treatments of choice for LM are surgical excision and Mohs micrographic operation, both of which provide a high cure rate and a low recurrence rate. 1 Other therapeutic approaches include cryotherapy; curettage and electrodessication; argon, carbon-dioxide, or Q-switched lasers; and radiotherapy. 1-5 A medical approach such as intralesional interferon alfa, topical azelaic acid, and imiquimod can be effective in older patients with compromised general conditions and in lesions that are difficult to excise because of their extension or location. [6][7][8] Tazarotene is an acetylenic retinoid highly selective for the ␤ and ␥ subtypes of retinoid acid receptors, whereas it does not bind to the retinoid X receptors. 9 Soon after its introduction for topical treatment of mild to moderate psoriasis, tazarotene 0.1% gel has been used to treat a variety of cutaneous diseases including congenital ichthyosis, Darier's disease, and basal cell carcinoma with good clinical response. [10][11][12] We report 2 patients with LM successfully treated with tazarotene 0.1% gel. CASE REPORTS Case 1An 80-year-old woman was examined for an asymptomatic, 3.8-ϫ 3-cm patch with variegate color ranging from pink to brown and black, located on the left zygomatic region (Fig 1, A). The lesion had been present for 10 years and previously treated with cryosurgery, and electrodessication and curettage. Dermoscopic analysis showed features highly suggestive of LM such as asymmetric pigmented follicular openings, rhomboidal structures, irregular pigmentation, and slate-gray dots/globules. Histopathologic examination of a 5-mm punch biopsy specimen, taken from the most pigmented area of the lesion, revealed atypical melanocytes, isolated and in small nests, located in the basal layer of the epidermis. Elastotic changes were present in the dermis. On the basis of the patient's refusal to undergo surgical excision, we proposed a topical treatment with once-daily tazarotene 0.1% gel. The patient was informed of the investigative nature of the treatment and written informed consent was obtained. Complete regression, clinically corresponding to disappearance of the lesion and dermoscopically...

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Topical imiquimod treatment of a cutaneous melanoma metastasis

Cited by 79 publications

References 0 publications

Identification and Characterization of pDC-Like Cells in Normal Mouse Skin and Melanomas Treated with Imiquimod

Identification and Characterization of pDC-Like Cells in Normal Mouse Skin and Melanomas Treated with Imiquimod

TLR7 and TLR8 as targets in cancer therapy

Treatment of lentigo maligna with tazarotene 0.1% gel

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